NR6A1

protein-coding

nuclear receptor subfamily 6 group A member 1, the group of Nuclear receptor subfamily 6 group A

Gene summary

This gene encodes an orphan nuclear receptor which is a member of the nuclear hormone receptor family. Its expression pattern suggests that it may be involved in neurogenesis and germ cell development. The protein can homodimerize and bind DNA, but in vivo targets have not been identified. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2013]

Previous symbols:

GCNF

MANE transcript

NM_033334.4

Inheritance

—

ClinVar variants

P:8U:66B:6

Top phenotype

Oculovertebral syndrome

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr9:124,517,275-124,771,311

External References & Databases

Ensembl (ENSG00000148200)

Transcript & Mutation Effects

hg38 • Region Span ~254.0 kb

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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 NR6A1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 59

Oculovertebral syndromeTotal: 10

not providedTotal: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Isolated anophthalmia-microphthalmia syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033334.4. 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			2 clinvar	2 clinvar	2 clinvar	6
missense	1 clinvar	2 clinvar	60 clinvar	1 clinvar	1 clinvar	65
nonsense	2 clinvar		1 clinvar			3
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	3	5	66	3	3	80

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033334.4	RefSeq	NP_201591.2	10	MANE Select
ENST00000487099.7	Ensembl	ENSP00000420267.1	10	MANE Select
NM_001278546.2	RefSeq	NP_001265475.1	10	Standard
NM_001410996.1	RefSeq	NP_001397925.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NHR
Gene expression (Transcription)
Generic Transcription Pathway
Nuclear Receptor transcription pathway
RNA Polymerase II Transcription

Biological Process

negative regulation of transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
gamete generation
spermatogenesis
cell population proliferation

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
steroid hormone receptor activity

Cellular Component

nucleus
nucleoplasm
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000487099
Coding exons: 10
Length: 254036
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125746
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.83	176	259	0.681	0.0000149	3143
Missense (PolyPhen)		46	109.37	0.42058		1201
Synonymous	-0.456	109	103	1.06	0.00000603	911
Loss of Function	4.12	3	25.4	0.118	0.00000141	284

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan nuclear receptor. Binds to a response element containing the sequence 5'-TCAAGGTCA-3'. May be involved in the regulation of gene expression in germ cell development during gametogenesis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.196

Intolerance Scores

LoFtool: 0.0544
RVIS EVS: -0.38
RVIS percentile EVS: 27.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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