SH3TC2

SH3 domain and tetratricopeptide repeats 2, the group of MicroRNA protein coding host genes|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 5:148923638-149063163

Links

ENSG00000169247 ∙ NCBI:79628 ∙ OMIM:608206 ∙ HGNC:29427 ∙ Uniprot:Q8TF17 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• susceptibility to mononeuropathy of the median nerve, mild (Limited), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 4C (Definitive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4C (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4C (Supportive), mode of inheritance: AR
• autosomal recessive hereditary demyelinating motor and sensory neuropathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, type 4C; Mononeuropathy of the median nerve, mild	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	Neurologic	14574644; 16326826; 16924012; 19744956; 20220177; 20301514; 20301641; 21291453; 22950825

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SH3TC2 gene.

• Charcot-Marie-Tooth disease type 4 (975 variants)
• Charcot-Marie-Tooth disease type 4C (587 variants)
• Susceptibility to mononeuropathy of the median nerve, mild (533 variants)
• not provided (351 variants)
• Inborn genetic diseases (235 variants)
• Charcot-Marie-Tooth disease (178 variants)
• not specified (66 variants)
• Mononeuropathy of the Median Nerve (56 variants)
• Charcot-Marie-Tooth disease type 4C;Susceptibility to mononeuropathy of the median nerve, mild (14 variants)
• Tip-toe gait (11 variants)
• Susceptibility to mononeuropathy of the median nerve, mild;Charcot-Marie-Tooth disease type 4C (6 variants)
• SH3TC2-Related Disorders (5 variants)
• SH3TC2-related condition (4 variants)
• Distal spinal muscular atrophy (4 variants)
• Hereditary motor and sensory neuropathy (2 variants)
• Charcot-Marie-Tooth disease, type I (2 variants)
• Peripheral neuropathy (2 variants)
• 7 conditions (1 variants)
• Tip-toe gait;Delayed speech and language development;limited range of motion of the upper ankle;Pes cavus (1 variants)
• Charcot-Marie-Tooth disease type 1B (1 variants)
• Hereditary spastic paraplegia (1 variants)
• Hereditary motor neuron disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SH3TC2 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			7	199	8	214
missense	1	10	475	25	5	516
nonsense	34	10	1			45
start loss		1				1
frameshift	30	9	4			43
inframe indel			12			12
splice donor/acceptor (+/-2bp)	4	14	1			19
splice region	1	3	20	15	1	40
non coding	1		311	185	98	595
Total	70	44	811	409	111

Highest pathogenic variant AF is 0.0000394

Variants in SH3TC2

This is a list of pathogenic ClinVar variants found in the SH3TC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-148982157-AT-A		Mononeuropathy of the Median Nerve • Charcot-Marie-Tooth disease type 4	Uncertain significance (Jun 14, 2016)
5-148982157-A-AT		Charcot-Marie-Tooth disease type 4 • Mononeuropathy of the Median Nerve	Likely benign (Jun 14, 2016)
5-148982157-A-ATT		Mononeuropathy of the Median Nerve • Charcot-Marie-Tooth disease type 4	Uncertain significance (Jun 14, 2016)
5-148982206-C-A		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Uncertain significance (Jan 13, 2018)
5-148982354-A-G		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Likely benign (Jan 13, 2018)
5-148982420-A-G		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Uncertain significance (Jan 13, 2018)
5-148982499-C-T		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Benign/Likely benign (Jan 13, 2018)
5-148982503-A-G		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Uncertain significance (Jan 13, 2018)
5-148982512-G-A		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Uncertain significance (Jan 13, 2018)
5-148982543-G-C		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Uncertain significance (Jan 13, 2018)
5-148982676-C-T		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Likely benign (Jan 13, 2018)
5-148982677-G-A		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Uncertain significance (Jan 12, 2018)
5-148982756-T-C		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Uncertain significance (Jan 13, 2018)
5-148982925-C-T		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Likely benign (Apr 17, 2022)
5-148982983-A-G		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Likely benign (Jan 13, 2018)
5-148983008-C-T		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Uncertain significance (Jan 12, 2018)
5-148983053-T-C		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Conflicting classifications of pathogenicity (Jan 13, 2018)
5-148983172-A-G		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Uncertain significance (Jan 13, 2018)
5-148983179-G-T		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Uncertain significance (Jan 13, 2018)
5-148983225-CGTTT-C		Mononeuropathy of the Median Nerve • Charcot-Marie-Tooth disease type 4	Likely benign (May 16, 2021)
5-148983239-T-C		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Benign/Likely benign (May 22, 2021)
5-148983316-A-G		Charcot-Marie-Tooth disease type 4 • Mononeuropathy of the Median Nerve	Uncertain significance (Jun 14, 2016)
5-148983340-T-C		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Uncertain significance (Jan 12, 2018)
5-148983430-A-C		Charcot-Marie-Tooth disease type 4C • Susceptibility to mononeuropathy of the median nerve, mild	Uncertain significance (Jan 12, 2018)
5-148983562-T-C		Susceptibility to mononeuropathy of the median nerve, mild • Charcot-Marie-Tooth disease type 4C	Conflicting classifications of pathogenicity (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SH3TC2	protein_coding	protein_coding	ENST00000515425	17	139525

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.34e-16	0.990	125451	0	297	125748	0.00118

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.713	721	669	1.08	0.0000386	8347
Missense in Polyphen		188	187.03	1.0052		2425
Synonymous	-1.40	307	277	1.11	0.0000151	2631
Loss of Function	2.67	33	54.3	0.608	0.00000274	663

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00118	0.00118
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000326	0.000326
Finnish	0.000693	0.000693
European (Non-Finnish)	0.00181	0.00180
Middle Eastern	0.000326	0.000326
South Asian	0.00108	0.00108
Other	0.00179	0.00179

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Mononeuropathy of the median nerve mild (MNMN) [MIM:613353]: A disease characterized by median nerve mononeuropathy at the wrist. The clinical presentation ranges from a mild phenotype, consistent with carpal tunnel syndrome, to a severe median nerve mononeuropathy at the wrist associated with evidence of a more widespread axonal polyneuropathy. The latter phenotype is similar to that of patients with hereditary neuropathy with liability to pressure palsies. {ECO:0000269|PubMed:20220177}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.477
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.23

Haploinsufficiency Scores

• pHI: 0.134
• hipred: N
• hipred_score: 0.199
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.368

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sh3tc2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: peripheral nervous system myelin maintenance;regulation of intracellular protein transport;regulation of ERBB signaling pathway
• Cellular component: plasma membrane;cytoplasmic vesicle