TM9SF2

protein-coding

transmembrane 9 superfamily member 2, the group of Transmembrane 9 superfamily members

Gene summary

This gene encodes a member of the transmembrane 9 superfamily. The encoded 76 kDa protein localizes to early endosomes in human cells. The encoded protein possesses a conserved and highly hydrophobic C-terminal domain which contains nine transmembrane domains. The protein may play a role in small molecule transport or act as an ion channel. A pseudogene associated with this gene is located on the X chromosome. [provided by RefSeq, Oct 2012]

MANE transcript

NM_004800.3

Inheritance

—

ClinVar variants

U:56B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr13:99,446,311-99,564,048

External References & Databases

Ensembl (ENSG00000125304)

Transcript & Mutation Effects

hg38 • Region Span ~117.7 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 TM9SF2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 48

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004800.3. 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			4 clinvar			4
missense			50 clinvar	3 clinvar		53
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	56	3	0	59

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004800.3	RefSeq	NP_004791.1	17	MANE Select
ENST00000376387.5	Ensembl	ENSP00000365567.3	17	MANE Select
ENST00000642146.1	Ensembl	ENSP00000494275.1	1	Standard
ENST00000642475.1	Ensembl	ENSP00000493515.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein localization to membrane

Cellular Component

endosome
integral component of plasma membrane
endosome membrane
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376387
Coding exons: 17
Length: 62590
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125733
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.27	189	365	0.518	0.0000183	4361
Missense (PolyPhen)		41	159.7	0.25674		1933
Synonymous	-0.248	137	133	1.03	0.00000704	1246
Loss of Function	5.70	0	37.8	0.00	0.00000184	458

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: In the intracellular compartments, may function as a channel or small molecule transporter.;

Recessive Scores

pRec: 0.0938

Intolerance Scores

LoFtool: 0.243
RVIS EVS: -0.8
RVIS percentile EVS: 12.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.645

Gene Damage Prediction

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