SH3TC2

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

Basic information

Region (hg38): 5:148923639-149063163

Links

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

Phenotypes

GenCC

Source: genCC

• autosomal recessive hereditary demyelinating motor and sensory neuropathy (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
• susceptibility to mononeuropathy of the median nerve, mild (Limited), mode of inheritance: AD
• susceptibility to mononeuropathy of the median nerve, mild (Strong), mode of inheritance: AR
• susceptibility to mononeuropathy of the median nerve, mild (Limited), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 4C (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 (1064 variants)
• Inborn_genetic_diseases (320 variants)
• not_provided (311 variants)
• Charcot-Marie-Tooth_disease (193 variants)
• Charcot-Marie-Tooth_disease_type_4C (185 variants)
• Susceptibility_to_mononeuropathy_of_the_median_nerve,_mild (120 variants)
• not_specified (109 variants)
• SH3TC2-related_disorder (35 variants)
• Tip-toe_gait (11 variants)
• Charcot-Marie-Tooth_disease,_type_I (6 variants)
• Distal_spinal_muscular_atrophy (4 variants)
• Mononeuropathy_of_the_Median_Nerve (3 variants)
• Hereditary_motor_and_sensory_neuropathy (2 variants)
• Upper_limb_undergrowth (1 variants)
• Peripheral_neuropathy (1 variants)
• Short_lower_limbs (1 variants)
• Schizophrenia (1 variants)
• Autosomal_dominant_intermediate_Charcot-Marie-Tooth_disease (1 variants)
• Delayed_speech_and_language_development (1 variants)
• Charcot-Marie-Tooth_disease_type_1B (1 variants)
• Scoliosis (1 variants)
• Pes_cavus (1 variants)
• Arthrogryposis_multiplex_congenita (1 variants)
• Decreased_muscle_mass (1 variants)
• limited_range_of_motion_of_the_upper_ankle (1 variants)
• Hereditary_motor_neuron_disease (1 variants)
• Hemihypertrophy (1 variants)
• Hereditary_spastic_paraplegia (1 variants)
• Congenital_contracture (1 variants)
• Ependymoma (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. These statistics are base on transcript: NM_000024577.4. 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	1		5	295	9	310
missense	1	23	560	97	1	682
nonsense	44	17	4			65
start loss		1				1
frameshift	44	16	14			74
splice donor/acceptor (+/-2bp)	8	17	2			27
Total	98	74	585	392	10

Highest pathogenic variant AF is 0.0010427419

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
		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

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

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