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transcription factor 12

Summary

Gene Symbol

TCF12

Organism

Homo sapiens (human)

External Links

NCBI Gene

6938

PubChem

6938

Alliance of Genome Resources

HGNC:11623

Annotation

Keyword

3D-structure
Alternative splicing
Craniosynostosis
DNA-binding
Developmental protein
Differentiation
Disease variant
Hypogonadotropic hypogonadism
Isopeptide bond
Kallmann syndrome
Neurogenesis
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Transcription regulation
Ubl conjugation

Proteins

Displaying **all 2** entries
UniProt	Protein Name
Q99081	Class B basic helix-loop-helix protein 20 DNA-binding protein HTF4 E-box-binding protein Transcription factor HTF-4
F5GY10	DNA-binding protein HTF4 E-box-binding protein Transcription factor HTF-4

Annotation information from UniProt.

Gene Ontology (GO)

Displaying entries **1 - 5** of 10 in total

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GO Term	Evidence Code	PMID
regulation of transcription by RNA polymerase II	IBA
immune response	TAS	1312219
nervous system development	IEA
muscle organ development	TAS	1312219
gene expression	IEA

GO Hierarchy

biological process

immune system process [inference]

immune response

metabolic process [inference]

biosynthetic process [inference]

cellular biosynthetic process [inference]

macromolecule biosynthetic process [inference]

gene expression

organic substance biosynthetic process [inference]

macromolecule biosynthetic process [inference]

gene expression

cellular metabolic process [inference]

cellular biosynthetic process [inference]

macromolecule biosynthetic process [inference]

gene expression

organic substance metabolic process [inference]

macromolecule metabolic process [inference]

macromolecule biosynthetic process [inference]

gene expression

organic substance biosynthetic process [inference]

macromolecule biosynthetic process [inference]

gene expression

cellular process [inference]

cellular metabolic process [inference]

cellular biosynthetic process [inference]

macromolecule biosynthetic process [inference]

gene expression

cellular developmental process [inference]

cell differentiation

developmental process [inference]

anatomical structure development [inference]

animal organ development [inference]

muscle organ development

system development [inference]

nervous system development

muscle structure development [inference]

muscle organ development

cellular developmental process [inference]

cell differentiation

response to stimulus [inference]

immune response

response to endogenous stimulus [inference]

response to hormone [inference]

response to peptide hormone [inference]

response to gonadotropin-releasing hormone

response to chemical [inference]

response to organic substance [inference]

response to hormone [inference]

response to peptide hormone [inference]

response to gonadotropin-releasing hormone

response to organonitrogen compound [inference]

response to peptide [inference]

response to peptide hormone [inference]

response to gonadotropin-releasing hormone

response to nitrogen compound [inference]

response to organonitrogen compound [inference]

response to peptide [inference]

response to peptide hormone [inference]

response to gonadotropin-releasing hormone

response to oxygen-containing compound [inference]

response to peptide [inference]

response to peptide hormone [inference]

response to gonadotropin-releasing hormone

biological regulation [inference]

regulation of biological process [inference]

regulation of metabolic process [inference]

regulation of biosynthetic process [inference]

positive regulation of biosynthetic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of cellular biosynthetic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of gene expression

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of metabolic process [inference]

positive regulation of biosynthetic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of macromolecule metabolic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cellular metabolic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nitrogen compound metabolic process [inference]

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of cellular metabolic process [inference]

regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cellular metabolic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of cellular biosynthetic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of gene expression

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of nitrogen compound metabolic process [inference]

regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nitrogen compound metabolic process [inference]

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of macromolecule metabolic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of gene expression

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of macromolecule metabolic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of primary metabolic process [inference]

regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of biological process [inference]

positive regulation of metabolic process [inference]

positive regulation of biosynthetic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of macromolecule metabolic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cellular metabolic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nitrogen compound metabolic process [inference]

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cellular process [inference]

positive regulation of cellular metabolic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cell differentiation [inference]

positive regulation of neuron differentiation

positive regulation of developmental process [inference]

positive regulation of cell differentiation [inference]

positive regulation of neuron differentiation

regulation of developmental process [inference]

regulation of cell differentiation [inference]

positive regulation of cell differentiation [inference]

positive regulation of neuron differentiation

regulation of neuron differentiation [inference]

positive regulation of neuron differentiation

positive regulation of developmental process [inference]

positive regulation of cell differentiation [inference]

positive regulation of neuron differentiation

regulation of cellular process [inference]

regulation of cellular metabolic process [inference]

regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cellular metabolic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of cellular biosynthetic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of gene expression

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II

positive regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

regulation of cell differentiation [inference]

positive regulation of cell differentiation [inference]

positive regulation of neuron differentiation

regulation of neuron differentiation [inference]

positive regulation of neuron differentiation

positive regulation of cellular process [inference]

positive regulation of cellular metabolic process [inference]

positive regulation of cellular biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of gene expression

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of nucleobase-containing compound metabolic process [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of transcription by RNA polymerase II

positive regulation of cell differentiation [inference]

positive regulation of neuron differentiation

Displaying entries **1 - 5** of 11 in total

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GO Term	Evidence Code	PMID
chromatin	ISA
chromatin	IDA	21828274
chromatin	IBA
nucleus	IDA	21828274
nucleoplasm	TAS

GO Hierarchy

cellular component

protein-containing complex [inference]

transcription regulator complex

RNA polymerase II transcription regulator complex

protein-DNA complex [inference]

chromatin

nuclear protein-containing complex [inference]

RNA polymerase II transcription regulator complex

cellular anatomical entity [inference]

nuclear body [inference]

nuclear speck

organelle [inference]

membrane-bounded organelle [inference]

intracellular membrane-bounded organelle

nucleus

intracellular organelle [inference]

intracellular membrane-bounded organelle

nucleus

Displaying entries **1 - 5** of 17 in total

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GO Term	Evidence Code	PMID
transcription cis-regulatory region binding	IDA	11802795
RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	11802795
RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
DNA-binding transcription factor activity, RNA polymerase II-specific	IBA

GO Hierarchy

molecular function

binding [inference]

protein binding

transcription factor binding [inference]

DNA-binding transcription factor binding

bHLH transcription factor binding

protein domain specific binding [inference]

HMG box domain binding

SMAD binding

protein dimerization activity [inference]

protein heterodimerization activity

organic cyclic compound binding [inference]

nucleic acid binding [inference]

transcription regulatory region nucleic acid binding [inference]

transcription cis-regulatory region binding

RNA polymerase II transcription regulatory region sequence-specific DNA binding [inference]

RNA polymerase II cis-regulatory region sequence-specific DNA binding

cis-regulatory region sequence-specific DNA binding

RNA polymerase II cis-regulatory region sequence-specific DNA binding

DNA binding [inference]

double-stranded DNA binding [inference]

sequence-specific double-stranded DNA binding

transcription cis-regulatory region binding

RNA polymerase II transcription regulatory region sequence-specific DNA binding [inference]

RNA polymerase II cis-regulatory region sequence-specific DNA binding

cis-regulatory region sequence-specific DNA binding

RNA polymerase II cis-regulatory region sequence-specific DNA binding

sequence-specific DNA binding [inference]

sequence-specific double-stranded DNA binding

transcription cis-regulatory region binding

RNA polymerase II transcription regulatory region sequence-specific DNA binding [inference]

RNA polymerase II cis-regulatory region sequence-specific DNA binding

cis-regulatory region sequence-specific DNA binding

RNA polymerase II cis-regulatory region sequence-specific DNA binding

transcription regulator activity [inference]

DNA-binding transcription factor activity

DNA-binding transcription factor activity, RNA polymerase II-specific

DNA-binding transcription activator activity, RNA polymerase II-specific

DNA-binding transcription activator activity [inference]

DNA-binding transcription activator activity, RNA polymerase II-specific

Gene Ontology information from NCBI Gene and UniProt.

OrthoDB (Group)

Group level

Eukaryota

Group Name

Transcription factor 12

Functional Category

E: Amino acid transport and metabolism
G: Carbohydrate transport and metabolism
T: Signal transduction mechanisms

Displaying 1 entry
Gene Ontology
protein dimerization activity

Displaying **all 2** entries
InterPro
Helix-loop-helix DNA-binding domain superfamily
Myc-type, basic helix-loop-helix (bHLH) domain

Disease

Disease Ontology

Displaying **all 2** entries
DO ID	Disease Name	Source
DOID:0090070	hypogonadotropic hypogonadism	Alliance of Genome Resources
DOID:2340	craniosynostosis	Alliance of Genome Resources

Ortholog

Displaying entries **11 - 20** of **102** in total

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Species	Gene ID	Orthologous MAtrix
Monodelphis domestica	100020031	MONDO02189
Equus caballus	100068843	HORSE16059
Ornithorhynchus anatinus	100083476	ORNAN26596
Taeniopygia guttata	100226398	TAEGU02297
Ictalurus punctatus	100304623	ICTPU22086
Ictalurus punctatus	100329230	ICTPU22086
Oryctolagus cuniculus	100339415	RABIT06027
Pongo abelii	100460448	PONAB09043
Ailuropoda melanoleuca	100469676	AILME11324
Nomascus leucogenys	100603993	NOMLE32164

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OrthoDB (Group)

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Acknowledgements