CRISPLD2

Chr 16

cysteine rich secretory protein LCCL domain containing 2

Also known as: CRISP11, LCRISP2, LGL1

NCBI Gene: 83716 ENSG00000103196 UniProt: Q9H0B8 OMIM: 612434

The CRISPLD2 protein promotes matrix assembly and is involved in face morphogenesis through glycosaminoglycan binding activity. Mutations cause autosomal recessive nasopharyngeal teratoma, affecting craniofacial development. The gene shows minimal constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable glycosaminoglycan binding activity. Involved in face morphogenesis. Located in transport vesicle. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.86

Clinical Summary— CRISPLD2

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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

123 VUS of 183 total submissions

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?

0.86LOEUF

pLI 0.000

Z-score 2.17

OE 0.58 (0.40–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.60Z-score

OE missense 1.26 (1.16–1.36)

390 obs / 310.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.58 (0.40–0.86)

0≤0.351.4

Missense OE?1.26 (1.16–1.36)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 18 / 31.1Missense obs/exp: 390 / 310.6Syn Z: -2.47

This gene — mechanism propensity

0.6648th %ile

GOF

0.5857th %ile

LOF

0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

183 submitted variants in ClinVar

ClinVar

Classification Summary

VUS123

Likely Benign20

Benign12

123

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	123	0	0	123
Likely Benign	5	5	10	20
Benign	3	4	5	12
Total	131	9	15	155

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

View in ClinVar →

46 pathogenic / likely-pathogenic (of 66) ClinVar copy-number / structural variants overlap CRISPLD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →