TSPAN12

tetraspanin 12, the group of Tetraspanins

Basic information

Region (hg38): 7:120787319-120858402

Previous symbols: [ "TM4SF12" ]

Links

ENSG00000106025 ∙ NCBI:23554 ∙ OMIM:613138 ∙ HGNC:21641 ∙ Uniprot:O95859 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• exudative vitreoretinopathy 5 (Strong), mode of inheritance: AD
• exudative vitreoretinopathy (Supportive), mode of inheritance: AD
• exudative vitreoretinopathy 5 (Strong), mode of inheritance: AD
• TSPAN12-related vitreoretinopathy (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Exudative vitreoretinopathy 5; Retinal dysplasia and severe familial exudative vitreoretinopathy	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	20159111; 20159112; 20301326; 21334594; 21552475; 22427576

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TSPAN12 gene.

• not provided (174 variants)
• Exudative vitreoretinopathy 5 (57 variants)
• Familial exudative vitreoretinopathy (7 variants)
• Inborn genetic diseases (6 variants)
• not specified (2 variants)
• Retinal dystrophy (2 variants)
• Atrophia bulborum hereditaria (1 variants)
• TSPAN12-related condition (1 variants)
• Persistent hyperplastic primary vitreous, autosomal recessive (1 variants)
• Vitreoretinopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSPAN12 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			1	25	2	28
missense	2	2	83	1	2	90
nonsense	5		1			6
start loss	1					1
frameshift	7	2				9
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	3				5
splice region			5	7	1	13
non coding			20	12	22	54
Total	17	7	107	38	26

Highest pathogenic variant AF is 0.00000658

Variants in TSPAN12

This is a list of pathogenic ClinVar variants found in the TSPAN12 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-120787322-A-C		Exudative vitreoretinopathy 5	Benign (Jan 12, 2018)
7-120787349-T-A		Exudative vitreoretinopathy 5	Benign (Jan 13, 2018)
7-120787352-T-C		Exudative vitreoretinopathy 5	Uncertain significance (Apr 27, 2017)
7-120787453-T-A		Exudative vitreoretinopathy 5	Benign (Jan 13, 2018)
7-120787523-CAT-C		Familial exudative vitreoretinopathy	Likely benign (Jun 14, 2016)
7-120787594-C-T		Exudative vitreoretinopathy 5	Benign (Jan 13, 2018)
7-120787705-G-C		Exudative vitreoretinopathy 5	Uncertain significance (Jan 13, 2018)
7-120788039-G-C		Exudative vitreoretinopathy 5	Uncertain significance (Jan 12, 2018)
7-120788258-T-A		Exudative vitreoretinopathy 5	Benign (Jan 12, 2018)
7-120788263-C-T		Exudative vitreoretinopathy 5	Uncertain significance (Jan 12, 2018)
7-120788466-A-G		Exudative vitreoretinopathy 5	Uncertain significance (Jan 12, 2018)
7-120788488-G-T		Exudative vitreoretinopathy 5	Uncertain significance (Jan 13, 2018)
7-120788489-G-T		Exudative vitreoretinopathy 5	Uncertain significance (Jan 13, 2018)
7-120788552-A-G		Exudative vitreoretinopathy 5	Likely benign (Jan 13, 2018)
7-120788553-G-A		Exudative vitreoretinopathy 5	Benign (Sep 10, 2021)
7-120788593-TA-T			Uncertain significance (Aug 21, 2022)
7-120788597-ACTC-A			Uncertain significance (Aug 10, 2022)
7-120788601-C-T			Likely benign (Aug 24, 2023)
7-120788605-A-C			Uncertain significance (Jan 25, 2024)
7-120788613-G-T			Uncertain significance (May 26, 2022)
7-120788628-G-C			Uncertain significance (Dec 01, 2021)
7-120788633-C-T			Uncertain significance (Nov 21, 2022)
7-120788635-A-G		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
7-120788635-A-T			Uncertain significance (May 20, 2020)
7-120788640-T-C			Likely benign (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSPAN12	protein_coding	protein_coding	ENST00000222747	7	71081

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.695	0.305	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.767	131	158	0.828	0.00000742	2003
Missense in Polyphen		33	44.737	0.73764		563
Synonymous	-0.0435	56	55.6	1.01	0.00000268	564
Loss of Function	3.14	3	17.0	0.177	7.24e-7	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000301	0.000300
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of cell surface receptor signal transduction. Plays a central role in retinal vascularization by regulating norrin (NDP) signal transduction. Acts in concert with norrin (NDP) to promote FZD4 multimerization and subsequent activation of FZD4, leading to promote accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated transcriptional programs. Suprisingly, it only activate the norrin (NDP)-dependent activation of FZD4, while it does not activate the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1) (By similarity). Acts as a regulator of membrane proteinases such as ADAM10 and MMP14/MT1-MMP. Activates ADAM10-dependent cleavage activity of amyloid precursor protein (APP). Activates MMP14/MT1-MMP-dependent cleavage activity. {ECO:0000250, ECO:0000269|PubMed:19211836, ECO:0000269|PubMed:19587294}.
• Disease: DISEASE: Vitreoretinopathy, exudative 5 (EVR5) [MIM:613310]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. {ECO:0000269|PubMed:20159111, ECO:0000269|PubMed:20159112, ECO:0000269|PubMed:22427576}. Note=The disease is caused by mutations affecting the gene represented in this entry. TSPAN12 dominant and recessive mutations have been identified in patients with exudative vitreoretinopathy. Patients with mutations in both alleles of TSPAN12 have severe exudative vitreoretinopathy or retinal dysplasia. These mutations appear to result in a milder phenotype in heterozygous mutation carriers (PubMed:22427576). {ECO:0000269|PubMed:22427576}.

Recessive Scores

• pRec: 0.0790

Intolerance Scores

• loftool: 0.456
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

• pHI: 0.500
• hipred: Y
• hipred_score: 0.644
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.398

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tspan12
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; hearing/vestibular/ear phenotype

Gene ontology

• Biological process: angiogenesis;cell surface receptor signaling pathway;retina layer formation;Wnt signaling pathway;regulation of angiogenesis
• Cellular component: integral component of plasma membrane;membrane;integral component of membrane
• Molecular function: protein binding;Wnt-activated receptor activity