SMPX

Chr XXLDXLR

small muscle protein X-linked

Also known as: Chisel, Csl, DFN6, DFNX4, MPD7

NCBI Gene: 23676 ENSG00000091482 UniProt: Q9UHP9 OMIM: 300226

The protein encoded by this gene is involved in coordinating muscle cell structural and functional states during growth, adaptation, and repair, and may help maintain inner ear cells under mechanical stress. Mutations cause X-linked deafness-4 and adult-onset distal myopathy, indicating involvement of both auditory and skeletal muscle systems. The gene shows X-linked inheritance with both dominant and recessive patterns reported.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a small protein that has no known functional domains. Mutations in this gene are a cause of X-linked deafness-4, and the encoded protein may play a role in the maintenance of inner ear cells subjected to mechanical stress. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

XLD/XLRLOEUF 0.952 OMIM phenotypes

Clinical Summary— SMPX

🧬

Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

19 unique Pathogenic / Likely Pathogenic· 37 VUS of 100 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — SMPX

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.95LOEUF

pLI 0.623

Z-score 1.63

OE 0.00 (0.00–0.95)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

-0.04Z-score

OE missense 1.02 (0.78–1.36)

34 obs / 33.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.95)

0≤0.351.4

Missense OE?1.02 (0.78–1.36)

0≤0.61.4

Synonymous OE?1.52

0≤1.21.6

LoF obs/exp: 0 / 3.1Missense obs/exp: 34 / 33.3Syn Z: -1.47

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic9

VUS37

Likely Benign21

Benign6

Conflicting3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	3	1	0	10
Likely Pathogenic	8	1	0	0	9
VUS	2	26	9	0	37
Likely Benign	0	0	10	11	21
Benign	0	1	5	0	6
Conflicting	—				3
Total	16	31	25	11	86

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

93 pathogenic / likely-pathogenic (of 100) ClinVar copy-number / structural variants overlap SMPX — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →