TM9SF4

protein-coding

transmembrane 9 superfamily member 4, the group of Transmembrane 9 superfamily members

Gene summary

Involved in several processes, including positive regulation of protein localization; response to hypoxia; and vacuolar proton-transporting V-type ATPase complex assembly. Located in Golgi apparatus and early endosome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014742.4

Inheritance

ClinVar variants

U:63B:5

Top phenotype

TM9SF4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr20:32,109,714-32,167,258

External References & Databases

Ensembl (ENSG00000101337)

Transcript & Mutation Effects

hg38 • Region Span ~57.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TM9SF4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 49

TM9SF4-related disorderTotal: 3

not providedTotal: 2

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014742.4. 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			2 clinvar	2 clinvar		4
missense			51 clinvar	3 clinvar		54
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	63	5	0	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 68 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014742.4	RefSeq	NP_055557.2	18	MANE Select
ENST00000398022.7	Ensembl	ENSP00000381104.2	18	MANE Select
NM_001363731.2	RefSeq	NP_001350660.1	17	Standard
ENST00000217315.9	Ensembl	ENSP00000217315.5	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

response to hypoxia
phagocytosis
cell adhesion
regulation of intracellular pH
vacuolar proton-transporting V-type ATPase complex assembly

Molecular Function

protein binding

Cellular Component

early endosome
Golgi apparatus
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398022
Coding exons: 18
Length: 57753
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.96	233	399	0.583	0.0000244	4234
Missense (PolyPhen)		72	180.36	0.39921		1873
Synonymous	1.58	133	158	0.840	0.0000102	1212
Loss of Function	5.30	5	42.1	0.119	0.00000221	438

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Associates with proteins harboring glycine-rich transmembrane domains and ensures their efficient localization to the cell surface (PubMed:25999474). Regulates the assembly and activity of V-ATPase in colon cancer cells via its interaction with V-type proton ATPase subunit H (ATP6V1H) and contributes to V-ATPase-mediated pH alterations in cancer cells which play an important role in drug resistance and invasiveness of colon cancer cells (PubMed:25659576). Plays an important role in an atypical phagocytic activity of metastatic melanoma cells called cannibalism and is involved in the pH regulation of the intracellular vesicles in tumor cells (PubMed:19893578). {ECO:0000269|PubMed:19893578, ECO:0000269|PubMed:25659576, ECO:0000269|PubMed:25999474}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.136
RVIS EVS: -0.51
RVIS percentile EVS: 21.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.881

Gene Damage Prediction

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