TM9SF4

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

Basic information

Region (hg38): 20:32109713-32167258

Links

ENSG00000101337 ∙ NCBI:9777 ∙ OMIM:617727 ∙ HGNC:30797 ∙ Uniprot:Q92544 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TM9SF4 gene.

• Inborn genetic diseases (10 variants)
• TM9SF4-related condition (2 variants)
• not specified (1 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TM9SF4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			12	2		14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	12	2	0

Variants in TM9SF4

This is a list of pathogenic ClinVar variants found in the TM9SF4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-32109747-A-G		not specified	Likely benign (Jun 24, 2022)
20-32109751-C-T		not specified	Uncertain significance (Oct 14, 2023)
20-32133086-C-T		not specified	Uncertain significance (Nov 17, 2023)
20-32136120-A-T		not specified	Uncertain significance (Feb 27, 2024)
20-32136138-A-G		not specified	Uncertain significance (Jun 29, 2023)
20-32141553-A-G		not specified	Uncertain significance (Feb 21, 2024)
20-32141848-G-C		not specified	Uncertain significance (Dec 01, 2022)
20-32143008-C-A		not specified	Uncertain significance (Mar 07, 2024)
20-32143015-T-C		TM9SF4-related disorder	Uncertain significance (Jan 06, 2023)
20-32143025-G-A		not specified	Uncertain significance (Jan 24, 2024)
20-32143033-A-T		not specified	Uncertain significance (May 04, 2022)
20-32143069-C-T		not specified	Uncertain significance (Jan 06, 2023)
20-32143084-C-G		TM9SF4-related disorder	Uncertain significance (Dec 27, 2023)
20-32145169-A-T		not specified	Uncertain significance (Apr 22, 2022)
20-32146809-G-A		not specified	Uncertain significance (Nov 30, 2022)
20-32149688-C-A		not specified	Uncertain significance (Mar 21, 2023)
20-32150826-G-T		not specified	Uncertain significance (Mar 06, 2023)
20-32155166-G-A		not specified	Uncertain significance (Mar 07, 2024)
20-32157794-G-A		not specified	Uncertain significance (Feb 28, 2024)
20-32157875-G-A		Autism spectrum disorder	Likely benign (-)
20-32158482-G-A		not specified	Uncertain significance (Nov 29, 2023)
20-32160055-G-A		not specified	Uncertain significance (Jul 26, 2022)
20-32161283-G-A		not specified	Uncertain significance (Nov 06, 2023)
20-32161346-T-C		not specified	Uncertain significance (Jan 23, 2024)
20-32161361-A-C		not specified	Uncertain significance (Apr 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TM9SF4	protein_coding	protein_coding	ENST00000398022	18	57753

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000999	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.96	233	399	0.583	0.0000244	4234
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.279
• hipred: Y
• hipred_score: 0.673
• ghis: 0.632

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tm9sf4
• Phenotype: skeleton phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: response to hypoxia;phagocytosis;cell adhesion;regulation of intracellular pH;vacuolar proton-transporting V-type ATPase complex assembly;positive regulation of protein exit from endoplasmic reticulum;protein localization to membrane;positive regulation of protein localization to cell surface
• Cellular component: early endosome;Golgi apparatus;membrane;integral component of membrane
• Molecular function: protein binding