TMEM74B

protein-coding

transmembrane protein 74B

Gene summary

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C20orf46

MANE transcript

NM_001304748.2

Inheritance

—

ClinVar variants

U:34

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr20:1,180,561-1,185,415

External References & Databases

Ensembl (ENSG00000125895)

Transcript & Mutation Effects

hg38 • Region Span ~4.9 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 TMEM74B variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 34

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001304748.2. 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						0
missense			34 clinvar			34
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	34	0	0	34

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001304748.2	RefSeq	NP_001291677.1	2	MANE Select
ENST00000429036.2	Ensembl	ENSP00000400552.2	2	MANE Select
NM_001304749.2	RefSeq	NP_001291678.1	1	Standard
NM_001387329.1	RefSeq	NP_001374258.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381894
Coding exons: 2
Length: 4855
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125745
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.429	173	158	1.10	0.00000989	1605
Missense (PolyPhen)		61	63.839	0.95552		618
Synonymous	-0.190	75	72.9	1.03	0.00000466	600
Loss of Function	0.585	6	7.76	0.773	5.80e-7	72

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000064	0.000062	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.102

Intolerance Scores

RVIS EVS: -0.18
RVIS percentile EVS: 40.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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