IGHMBP2

Chr 11AR

immunoglobulin mu DNA binding protein 2

Also known as: CATF1, CMT2S, HCSA, HMN6, HMNR1, SMARD1, SMUBP2, ZFAND7

The protein is a helicase that binds specific DNA sequences in the immunoglobulin mu chain switch region. Mutations cause autosomal recessive spinal muscle atrophy with respiratory distress type 1, Charcot-Marie-Tooth disease axonal type 2S, and distal hereditary motor neuronopathy type 1. The pathogenic mechanism appears to involve dominant-negative effects.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.952 OMIM phenotypes
Clinical SummaryIGHMBP2
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Gene-Disease Validity (ClinGen)
hereditary peripheral neuropathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.000
Z-score 1.81
OE 0.71 (0.530.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.18Z-score
OE missense 0.98 (0.911.05)
580 obs / 592.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.71 (0.530.95)
00.351.4
Missense OE0.98 (0.911.05)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 31 / 43.9Missense obs/exp: 580 / 592.1Syn Z: -1.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveIGHMBP2-related spinal muscular atrophy with respiratory distressLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6646th %ile
GOF
0.5465th %ile
LOF
0.3162th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IGHMBP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗