CARHSP1

Chr 16

calcium regulated heat stable protein 1

Also known as: CRHSP-24, CRHSP24, CSDC1

NCBI Gene: 23589 ENSG00000153048 UniProt: Q9Y2V2 OMIM: 616885

The protein binds mRNA and regulates mRNA stability, with predicted roles in mRNA 3'-UTR binding and regulation of mRNA stability in the cytoplasm. Mutations cause autosomal recessive spastic paraplegia with intellectual disability, typically presenting in early childhood with progressive spasticity and developmental delays. The gene shows low constraint against loss-of-function variants, consistent with its autosomal recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Enables mRNA 3'-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in P granule; cytoplasmic exosome (RNase complex); and cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.87

Clinical Summary— CARHSP1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

50 VUS of 60 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.000

Z-score -0.35

OE 1.17 (0.62–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.38Z-score

OE missense 1.69 (1.48–1.91)

160 obs / 94.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.17 (0.62–1.87)

0≤0.351.4

Missense OE?1.69 (1.48–1.91)

0≤0.61.4

Synonymous OE?2.21

0≤1.21.6

LoF obs/exp: 6 / 5.1Missense obs/exp: 160 / 94.8Syn Z: -5.94

This gene — mechanism propensity

0.5771th %ile

GOF

0.6540th %ile

LOF

0.56top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

60 submitted variants in ClinVar

ClinVar

Classification Summary

VUS50

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	50	0	50
Likely Benign	0	1	1
Benign	0	0	0
Total	50	1	51

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 76) ClinVar copy-number / structural variants overlap CARHSP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →