TM4SF20

transmembrane 4 L six family member 20

Basic information

Region (hg38): 2:227362038-227381995

Links

ENSG00000168955 ∙ NCBI:79853 ∙ OMIM:615404 ∙ HGNC:26230 ∙ Uniprot:Q53R12 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• specific language impairment 5 (Limited), mode of inheritance: AD
• specific language impairment 5 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Specific language impairment 5	AD	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	Neurologic	23810381

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TM4SF20 gene.

• not_provided (53 variants)
• not_specified (30 variants)
• TM4SF20-related_disorder (7 variants)
• Specific_language_impairment_5 (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TM4SF20 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024795.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10	3	13
missense			44	7	3	54
nonsense			1			1
start loss						0
frameshift			2			2
splice donor/acceptor (+/-2bp)			3			3
Total	0	0	50	17	6

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TM4SF20	protein_coding	protein_coding	ENST00000304568	4	19840

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000186	0.486	125719	0	28	125747	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.396	131	119	1.10	0.00000550	1501
Missense in Polyphen		49	46.227	1.06		572
Synonymous	0.306	43	45.6	0.942	0.00000244	449
Loss of Function	0.340	6	6.97	0.861	2.94e-7	90

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.000307	0.000298
East Asian	0.0000552	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.0000552	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Polytopic transmembrane protein that inhibits regulated intramembrane proteolysis (RIP) of CREB3L1, inhibiting its activation and the induction of collagen synthesis (PubMed:25310401, PubMed:27499293). In response to ceramide, which alters TM4SF20 membrane topology, stimulates RIP activation of CREB3L1 (PubMed:27499293). Ceramide reverses the direction through which transmembrane helices are translocated into the endoplasmic reticulum membrane during translation of TM4SF20, this mechanism is called 'regulated alternative translocation' (RAT) and regulates the function of the transmembrane protein (PubMed:27499293). {ECO:0000269|PubMed:25310401, ECO:0000269|PubMed:27499293}.
• Disease: DISEASE: Specific language impairment 5 (SLI5) [MIM:615432]: A disorder characterized by a delay in early speech acquisition. It is usually associated with cerebral white matter abnormalities on brain MRI. Some individuals may show disorders in communication, consistent with autism spectrum disorder, or global developmental delay, although others ultimately show normal cognitive function. Penetrance is incomplete and expressivity is variable. {ECO:0000269|PubMed:23810381}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0835

Intolerance Scores

• loftool: 0.824
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.53

Haploinsufficiency Scores

• pHI: 0.115
• hipred: N
• hipred_score: 0.123

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tm4sf20

Gene ontology

• Biological process: negative regulation of proteolysis
• Cellular component: endoplasmic reticulum membrane;plasma membrane;focal adhesion;integral component of membrane