TM7SF3

protein-coding

transmembrane 7 superfamily member 3

Gene summary

Involved in cellular response to unfolded protein; negative regulation of programmed cell death; and positive regulation of insulin secretion. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_016551.3

Inheritance

—

ClinVar variants

U:84B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr12:26,971,579-27,014,434

External References & Databases

Ensembl (ENSG00000064115)

Transcript & Mutation Effects

hg38 • Region Span ~42.9 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 TM7SF3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016551.3. 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			76 clinvar	2 clinvar	1 clinvar	79
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	84	2	1	87

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 102 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016551.3	RefSeq	NP_057635.1	12	MANE Select
ENST00000343028.9	Ensembl	ENSP00000342322.4	12	MANE Select
ENST00000512808.2	Ensembl	ENSP00000440262.1	4	Standard
ENST00000535260.5	Ensembl	ENSP00000439318.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of insulin secretion
cellular response to unfolded protein
negative regulation of programmed cell death

Molecular Function

molecular_function

Cellular Component

plasma membrane
integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343028
Coding exons: 12
Length: 41240
Individuals with no LoFs: 125664
Homozygous LoFs: 0
Heterozygous LoFs: 83
Defined: 125747
p: 0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.893	262	306	0.856	0.0000153	3702
Missense (PolyPhen)		69	97.394	0.70846		1263
Synonymous	0.177	119	121	0.980	0.00000692	1138
Loss of Function	2.23	16	28.9	0.553	0.00000156	321

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.0011	0.00095	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00027	0.00021	rare
South Asian	0.00049	0.00049	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the inhibition of cytokine-induced death of pancreatic beta cells. Involved in the promotion of insulin secretion from pancreatic beta cells (PubMed:21853325). Is a downstream transcriptional target of p53/TP53, and acts as a pro- survival homeostatic factor that attenuates the development of cellular stress. Maintains protein homeostasis and promotes cell survival through attenuation of endoplasmic reticulum (ER) stress and the subsequent induction of unfolded protein response (UPR) (PubMed:27740623). {ECO:0000269|PubMed:21853325, ECO:0000269|PubMed:27740623}.;

Recessive Scores

pRec: 0.0953

Intolerance Scores

LoFtool: 0.791
RVIS EVS: -0.16
RVIS percentile EVS: 42.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.517

Gene Damage Prediction

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