CAMSAP1

Chr 9AR

calmodulin regulated spectrin associated protein 1

Also known as: CDCBM12

NCBI Gene: 157922 ENSG00000130559 UniProt: Q5T5Y3 OMIM: 613774

CAMSAP1 encodes a key microtubule-organizing protein that specifically binds and stabilizes the minus-ends of non-centrosomal microtubules, protecting them from depolymerization and regulating neurite outgrowth through spectrin interactions. Biallelic mutations cause autosomal recessive cortical dysplasia with other brain malformations, affecting cortical development and brain structure. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.24), reflecting its critical role in neurodevelopment.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables microtubule minus-end binding activity and spectrin binding activity. Involved in several processes, including neuron projection development; regulation of cell morphogenesis; and regulation of microtubule polymerization. Located in microtubule minus-end. Implicated in complex cortical dysplasia with other brain malformations. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.241 OMIM phenotype

Clinical Summary— CAMSAP1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 227 VUS of 294 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 1.000

Z-score 6.25

OE 0.13 (0.08–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.15Z-score

OE missense 0.80 (0.76–0.85)

763 obs / 949.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.13 (0.08–0.24)

0≤0.351.4

Missense OE?0.80 (0.76–0.85)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 8 / 60.4Missense obs/exp: 763 / 949.8Syn Z: -0.67

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateCAMSAP1-related neuronal migration disorderOTHERAR

This gene — mechanism propensity

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

0.3992th %ile

GOF

0.4578th %ile

LOF

0.68top 25%

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

294 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic6

VUS227

Likely Benign32

Benign4

Conflicting1

Likely Pathogenic

227

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	6	0	0	0	6
VUS	0	226	1	0	227
Likely Benign	0	21	2	9	32
Benign	0	1	0	3	4
Conflicting	—				1
Total	6	248	3	12	270

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

View in ClinVar →

61 pathogenic / likely-pathogenic (of 76) ClinVar copy-number / structural variants overlap CAMSAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →