HNF4G

protein-coding

hepatocyte nuclear factor 4 gamma, the group of Hepatocyte nuclear factor 4 family

Gene summary

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_004133.5

Inheritance

—

ClinVar variants

U:54B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr8:75,407,914-75,566,834

External References & Databases

Ensembl (ENSG00000164749)

Transcript & Mutation Effects

hg38 • Region Span ~158.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HNF4G variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004133.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			51 clinvar	1 clinvar		52
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	54	2	0	56

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004133.5	RefSeq	NP_004124.5	10	MANE Select
ENST00000396423.4	Ensembl	ENSP00000379701.3	10	MANE Select
NM_001330561.2	RefSeq	NP_001317490.1	9	Standard
ENST00000354370.5	Ensembl	ENSP00000346339.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Maturity onset diabetes of the young - Homo sapiens (human)
NHR
Gene expression (Transcription)
Generic Transcription Pathway
Nuclear Receptor transcription pathway

Biological Process

regulation of transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
intracellular receptor signaling pathway
steroid hormone mediated signaling pathway
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA-binding transcription factor activity
steroid hormone receptor activity

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396423
Coding exons: 10
Length: 158930
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125734
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.597	222	248	0.893	0.0000131	2944
Missense (PolyPhen)		51	84.963	0.60026		994
Synonymous	-1.06	96	83.7	1.15	0.00000431	810
Loss of Function	3.05	6	21.1	0.284	9.57e-7	274

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00030	0.00030	rare
South Asian	0.00036	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor. Has a lower transcription activation potential than HNF4-alpha.;

Recessive Scores

pRec: 0.228

Intolerance Scores

LoFtool: 0.214
RVIS EVS: -0.03
RVIS percentile EVS: 51.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium