TM7SF2

protein-coding

transmembrane 7 superfamily member 2

Gene summary

Enables Delta14-sterol reductase activity. Involved in cholesterol biosynthetic process. Located in endoplasmic reticulum. Part of signaling receptor complex. Is active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_003273.6

Inheritance

—

ClinVar variants

U:69B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr11:65,111,845-65,116,384

External References & Databases

Ensembl (ENSG00000149809)

Transcript & Mutation Effects

hg38 • Region Span ~4.5 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 TM7SF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003273.6. 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			62 clinvar			62
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	69	0	1	70

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003273.6	RefSeq	NP_003264.2	10	MANE Select
ENST00000279263.14	Ensembl	ENSP00000279263.7	10	MANE Select
NM_001277233.2	RefSeq	NP_001264162.1	9	Standard
ENST00000345348.10	Ensembl	ENSP00000329520.6	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Steroid biosynthesis - Homo sapiens (human)
Simvastatin Action Pathway
Pravastatin Action Pathway
Atorvastatin Action Pathway
Hyper-IgD syndrome

Biological Process

cholesterol biosynthetic process
sterol biosynthetic process
regulation of cholesterol biosynthetic process
oxidation-reduction process

Molecular Function

delta14-sterol reductase activity
NADP binding

Cellular Component

nuclear inner membrane
endoplasmic reticulum
endoplasmic reticulum membrane
integral component of plasma membrane
integral component of endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000279263
Coding exons: 10
Length: 4540
Individuals with no LoFs: 124759
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 124810
p: 0.000204

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.404	221	239	0.926	0.0000135	2600
Missense (PolyPhen)		103	123.42	0.83454		1349
Synonymous	0.339	101	105	0.958	0.00000586	916
Loss of Function	1.50	14	21.5	0.651	0.00000119	214

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00032	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00028	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00016	0.00016	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the conversion of lanosterol to cholesterol. {ECO:0000269|PubMed:11784322}.;

Intolerance Scores

RVIS EVS: -0.38
RVIS percentile EVS: 27.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.848

Gene Damage Prediction

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