CEP85L

Chr 6AD

centrosomal protein 85L

Also known as: C6orf204, LIS10, NY-BR-15, bA57K17.2

NCBI Gene: 387119 ENSG00000111860 UniProt: Q5SZL2 OMIM: 618865

The protein plays an essential role in neuronal cell migration during brain development. Mutations cause lissencephaly 10, a severe brain malformation disorder characterized by abnormal cortical development and intellectual disability. The condition follows an autosomal dominant inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene was identified as a breast cancer antigen. Nothing more is known of its function at this time. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.711 OMIM phenotype

Clinical Summary— CEP85L

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Gene-Disease Validity (ClinGen)

lissencephaly 10 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

29 unique Pathogenic / Likely Pathogenic· 220 VUS of 370 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?

0.71LOEUF

pLI 0.000

Z-score 3.09

OE 0.49 (0.35–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.40Z-score

OE missense 0.94 (0.87–1.03)

374 obs / 396.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.35–0.71)

0≤0.351.4

Missense OE?0.94 (0.87–1.03)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 21 / 42.8Missense obs/exp: 374 / 396.5Syn Z: -0.43

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCEP85L-related posterior-predominant lissencephalyLOFAD

This gene — mechanism propensity

0.6840th %ile

GOF

0.5758th %ile

LOF

0.4134th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

LOF41% of P/LP variants are LoF

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

ClinVar Variant Classifications

370 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic14

VUS220

Likely Benign67

Benign20

Conflicting13

Pathogenic

Likely Pathogenic

220

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	5	2	0	15
Likely Pathogenic	4	7	3	0	14
VUS	23	152	44	1	220
Likely Benign	0	22	17	28	67
Benign	0	3	17	0	20
Conflicting	—				13
Total	35	189	83	29	349

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap CEP85L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →