SMPX

small muscle protein X-linked

Basic information

Region (hg38): X:21705978-21758116

Previous symbols: [ "DFN6" ]

Links

ENSG00000091482 ∙ NCBI:23676 ∙ OMIM:300226 ∙ HGNC:11122 ∙ Uniprot:Q9UHP9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, X-linked 4 (Strong), mode of inheritance: XL
• hearing loss, X-linked 4 (Strong), mode of inheritance: XL
• X-linked nonsyndromic hearing loss (Supportive), mode of inheritance: XL
• myopathy, distal, 7, adult-onset, X-linked (Strong), mode of inheritance: XL
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, X-linked 4	XL	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment, which may occur in the prelingual stage in some individuals, may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Musculoskeletal	8872482; 21549336; 21549342; 21893181; 22911656; 33974137
Both prelingual and postlingual onset of deafness has been described, with males described as being affected earlier and more severely

ClinVar

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

• not_provided (56 variants)
• Hearing_loss,_X-linked_4 (15 variants)
• Myopathy,_distal,_7,_adult-onset,_X-linked (4 variants)
• not_specified (2 variants)
• Hearing_impairment (2 variants)
• SMPX-related_disorder (2 variants)
• Inborn_genetic_diseases (2 variants)
• X-linked_deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMPX gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014332.3. 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	11		12
missense	4		24		1	29
nonsense	5					5
start loss						0
frameshift	4	6	1			11
splice donor/acceptor (+/-2bp)	1	3	1			5
Total	14	9	27	11	1

Highest pathogenic variant AF is 0.0000132447

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMPX	protein_coding	protein_coding	ENST00000379494	3	52192

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.623	0.348	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0417	34	33.3	1.02	0.00000240	563
Missense in Polyphen		15	13.25	1.132		244
Synonymous	-1.47	20	13.2	1.52	0.00000110	172
Loss of Function	1.63	0	3.11	0.00	1.95e-7	60

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair. {ECO:0000250}.
• Disease: DISEASE: Deafness, X-linked, 4 (DFNX4) [MIM:300066]: A non- syndromic form of sensorineural, progressive hearing loss with postlingual onset. In affected males, the auditory impairment affects initially high-frequency hearing. It later evolves to become severe to profound and affects all frequencies. Carrier females manifest moderate hearing impairment in the high frequencies. {ECO:0000269|PubMed:21549336, ECO:0000269|PubMed:21549342, ECO:0000269|PubMed:22911656}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.421
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.323
• hipred: N
• hipred_score: 0.412
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smpx
• Phenotype: normal phenotype

Gene ontology

• Biological process: striated muscle contraction
• Cellular component: nucleus;muscle tendon junction;M band;costamere