CEP85L

protein-coding

centrosomal protein 85 like

Gene summary

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]

Previous symbols:

C6orf204

MANE transcript

NM_001042475.3

Inheritance

ClinVar variants

P:15U:127B:37

Top phenotype

Lissencephaly 10

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr6:118,460,772-118,710,075

External References & Databases

Ensembl (ENSG00000111860)

Transcript & Mutation Effects

hg38 • Region Span ~249.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lissencephaly 10STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030031

Submitter: Labcorp Genetics (formerly Invitae)

lissencephaly 10DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0030031

Submitter: G2P

lissencephaly 10DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0030031

Submitter: ClinGen

CEP85L was first reported in relation to autosomal dominant lissencephaly spectrum disorder (MONDO:0018838) in 2020 (Tsai et al., PMID: 32097630, Kodani et al., 32097629). The phenotypic spectrum includes developmental delay and seizures. Brain imaging shows features consistent with neuronal migration defects, including posterior-predominant lissencephaly, pachygyria, agyria, and subcortical band heterotopia. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism(s) AND/OR inheritance pattern AND/OR phenotypic variability. Therefore, the following disease entities have been lumped into one disease entity lissencephaly spectrum disorder (MONDO:0018838), AD. 17 variants (start codon, nonsense, splice and missense) that have been reported in 17 probands in 3 publications (PMID: 32097630, 32097629, 4440382) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is reported to be loss of function, and possibly dominant negative. This gene-disease relationship is also supported by experimental evidence, including animal models, and in vitro human stable cell lines (PMID: 32097630, 32097629). Mouse embryonic neuronal electroporation assays indicate reduced neuronal migration after shRNA knockdown of CEP85L. Human stable cell models (U2-OS) indicate reduced wound healing after siRNA knockdown of CEP85L. In summary, there is definitive evidence supporting the relationship between CEP85L and autosomal dominant lissencephaly spectrum disorder (MONDO:0018838). This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen brain malformations GCEP on the meeting date 9/24/2024, (SOP Version 11).

lissencephaly due to LIS1 mutationSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011830

Submitter: Illumina

Clinical Genomic Database (CGD)

Lissencephaly 10AD

Manifestation: Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: As with other genetic conditions that can involve seizures, knowledge of the genetic cause may be helpful for medication selection based on what has been beneficial in other patients

Refs: 32097630

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CEP85L variants in ClinVar

22 Conditions Cataloged

Dilated cardiomyopathy 1PTotal: 104

not providedTotal: 92

Inborn genetic diseasesTotal: 86

Cardiovascular phenotypeTotal: 44

Lissencephaly 10Total: 27

not specifiedTotal: 26

Hypertrophic cardiomyopathy 18Total: 22

CardiomyopathyTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001042475.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	14 clinvar		15
missense		7 clinvar	107 clinvar	22 clinvar	1 clinvar	137
nonsense		1 clinvar	6 clinvar			7
start loss	2 clinvar	1 clinvar				3
frameshift	1 clinvar		9 clinvar			10
splice donor/acceptor (+/-2bp)	3 clinvar		4 clinvar			7
Total	6	9	127	36	1	179

Highest pathogenic variant AF is 0.000019242801

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001042475.3	RefSeq	NP_001035940.1	13	MANE Select
ENST00000368491.8	Ensembl	ENSP00000357477.3	13	MANE Select
NM_001178035.2	RefSeq	NP_001171506.1	13	Standard
NM_206921.3	RefSeq	NP_996804.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

cytoplasm
centrosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368488
Coding exons: 13
Length: 249304
Individuals with no LoFs: 125706
Homozygous LoFs: 1
Heterozygous LoFs: 41
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.401	374	396	0.943	0.0000197	5306
Missense (PolyPhen)		110	142.48	0.77203		1948
Synonymous	-0.431	147	141	1.05	0.00000680	1437
Loss of Function	3.09	21	42.8	0.491	0.00000210	558

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00010	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00024	0.00023	rare
South Asian	0.00024	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0934

Intolerance Scores

RVIS EVS: 0.85
RVIS percentile EVS: 88.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium