SH3PXD2B

Chr 5AR

SH3 and PX domains 2B

Also known as: FAD49, FTHS, HOFI, KIAA1295, TKS4, TSK4

This adapter protein is essential for podosome formation and extracellular matrix degradation, binding matrix metalloproteinases and NADPH oxidases to organize reactive oxygen species generation. Biallelic mutations cause Frank-ter Haar syndrome, a rare autosomal recessive disorder affecting skeletal, cardiac, and other systems. The gene is highly constrained against loss-of-function variation (LOEUF 0.488), reflecting its critical cellular functions.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.491 OMIM phenotype
Clinical SummarySH3PXD2B
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Gene-Disease Validity (ClinGen)
Frank-Ter Haar syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.004
Z-score 4.08
OE 0.30 (0.190.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.53Z-score
OE missense 0.94 (0.871.01)
511 obs / 545.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.190.49)
00.351.4
Missense OE0.94 (0.871.01)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 12 / 39.8Missense obs/exp: 511 / 545.6Syn Z: 0.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSH3PXD2B-related Frank-ter Haar syndromeLOFAR

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

DN
0.7131th %ile
GOF
0.6247th %ile
LOF
0.3940th %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

SH3PXD2B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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