C4orf46

protein-coding

chromosome 4 open reading frame 46

Gene summary

This gene encodes a small, conserved protein of unknown function that is expressed in a variety of tissues. There are pseudogenes for this gene on chromosomes 6, 8, 16, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

MANE transcript

NM_001008393.4

Inheritance

—

ClinVar variants

U:3B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr4:158,666,675-158,672,255

External References & Databases

Ensembl (ENSG00000205208)

Transcript & Mutation Effects

hg38 • Region Span ~5.6 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 C4orf46 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001008393.4. 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					1 clinvar	1
missense			2 clinvar			2
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	3	0	1	4

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001008393.4	RefSeq	NP_001008394.1	2	MANE Select
ENST00000379205.5	Ensembl	ENSP00000368503.4	2	MANE Select
ENST00000508457.1	Ensembl	ENSP00000421533.1	2	Standard
ENST00000508457.2	Ensembl	ENSP00000421533.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379205
Coding exons: 2
Length: 5577
Individuals with no LoFs: 125426
Homozygous LoFs: 6
Heterozygous LoFs: 295
Defined: 125727
p: 0.00120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.239	62	56.9	1.09	0.00000294	705
Missense (PolyPhen)		28	27.892	1.0039		357
Synonymous	-0.617	28	24.1	1.16	0.00000117	244
Loss of Function	0.458	2	2.83	0.706	1.19e-7	41

Population LoF Frequency

Population	CAF	p-value	Status
African	0.035	0.017	notable
Latino/Admixed American	0.00081	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000098	0.000062	rare
South Asian	0	0.0	absent
Other	0.00065	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.407
RVIS EVS: 0.17
RVIS percentile EVS: 65.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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