CEP85L

Summary

CEP85L (centrosomal protein 85L, HGNC:21638) is a protein-coding gene on chromosome 6q22.31, encoding Centrosomal protein of 85 kDa-like (Q5SZL2). Plays an essential role in neuronal cell migration.

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.

Source: NCBI Gene 387119 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lissencephaly 10 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 331 total — 10 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 45
• MANE Select transcript: NM_001042475

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21638
Approved symbol	CEP85L
Name	centrosomal protein 85L
Location	6q22.31
Locus type	gene with protein product
Status	Approved
Aliases	NY-BR-15, bA57K17.2
Ensembl gene	ENSG00000111860
Ensembl biotype	protein_coding
OMIM	618865
Entrez	387119

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000360290, ENST00000368488, ENST00000368491, ENST00000392500, ENST00000419517, ENST00000434604, ENST00000462101, ENST00000472713, ENST00000476150, ENST00000483035, ENST00000489276, ENST00000875590, ENST00000875591

RefSeq mRNA: 3 — MANE Select: NM_001042475 NM_001042475, NM_001178035, NM_206921

CCDS: CCDS43498, CCDS5119, CCDS55052

Canonical transcript exons

ENST00000368491 — 13 exons

Exon	Start	End
ENSE00001870340	118651197	118651591
ENSE00001924835	118460772	118465568
ENSE00002140722	118470537	118470644
ENSE00002141238	118481779	118481933
ENSE00002151236	118511298	118511415
ENSE00002153960	118483706	118483858
ENSE00002159787	118469072	118469303
ENSE00002170224	118491686	118491865
ENSE00002180097	118479871	118479921
ENSE00002188529	118523802	118523920
ENSE00002195539	118480396	118480513
ENSE00003461500	118632453	118632611
ENSE00003613418	118565529	118566316

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 97.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6112 / max 255.1119, expressed in 1742 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75302	10.9612	1698
75305	4.3352	597
75300	0.5207	72
75303	0.4433	239
75301	0.1941	58
75304	0.0946	25
75299	0.0559	29
75298	0.0063	3

Top tissues by expression

255 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	97.07	gold quality
tibialis anterior	UBERON:0001385	95.49	gold quality
pylorus	UBERON:0001166	94.74	gold quality
dorsal root ganglion	UBERON:0000044	94.72	gold quality
trigeminal ganglion	UBERON:0001675	94.25	gold quality
deltoid	UBERON:0001476	93.94	gold quality
oviduct epithelium	UBERON:0004804	92.84	gold quality
adrenal tissue	UBERON:0018303	92.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.69	gold quality
left ventricle myocardium	UBERON:0006566	92.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.41	gold quality
left testis	UBERON:0004533	91.26	gold quality
testis	UBERON:0000473	91.23	gold quality
right testis	UBERON:0004534	91.06	gold quality
quadriceps femoris	UBERON:0001377	91.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.99	gold quality
biceps brachii	UBERON:0001507	90.98	gold quality
sural nerve	UBERON:0015488	90.78	gold quality
cardia of stomach	UBERON:0001162	90.74	gold quality
vastus lateralis	UBERON:0001379	90.58	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.39	gold quality
buccal mucosa cell	CL:0002336	90.28	gold quality
cerebellar vermis	UBERON:0004720	89.94	gold quality
myocardium	UBERON:0002349	89.88	gold quality
skeletal muscle tissue	UBERON:0001134	89.71	gold quality
visceral pleura	UBERON:0002401	89.69	gold quality
parietal pleura	UBERON:0002400	89.42	gold quality
tonsil	UBERON:0002372	89.20	gold quality
endothelial cell	CL:0000115	89.02	gold quality
superior surface of tongue	UBERON:0007371	88.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

258 targeting CEP85L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115

Literature-anchored findings (GeneRIF, showing 5)

• Detection of a novel imatinib-sensitive C6orf204-PDGFRB fusion in a patient with precursor T lymphoblastic lymphoma (T-ALL) and an associated myeloproliferative neoplasm with eosinophilia. (PMID:21938754)
• Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5. (PMID:32097629)
• Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly. (PMID:32097630)
• LRP8 (rs5177) and CEP85L (rs11756438) are contributed to schizophrenia susceptibility in Iranian population. (PMID:33079740)
• Further characterization of CEP85L-associated lissencephaly type 10: Report of a three-generation family and review of the literature. (PMID:37621218)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep85l	ENSDARG00000020777
mus_musculus	Cep85l	ENSMUSG00000038594
rattus_norvegicus	Cep85l	ENSRNOG00000000414

Paralogs (1): CEP85 (ENSG00000130695)

Protein

Protein identifiers

Centrosomal protein of 85 kDa-like — Q5SZL2 (reviewed: Q5SZL2)

Alternative names: Serologically defined breast cancer antigen NY-BR-15

All UniProt accessions (2): Q5SZL2, A2A3P3

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in neuronal cell migration.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Isoform 1 and isoform 4 are expressed in spleen, lymph, thymus, tonsil and peripheral blood leukocytes, with isoform 1 expressed at higher levels. Isoform 4 is detected in K-562 leukemia cells and in the blood of precursor T lymphoblastic lymphoma (T-ALL) patients.

Disease relevance. A chromosomal aberration involving CEP85L is found in a patient with T-lymphoblastic lymphoma (T-ALL) and an associated myeloproliferative neoplasm (MPN) with eosinophilia. Translocation t(5;6)(q33-34;q23) with PDGFRB. The translocation fuses the 5’-end of CEP85L (isoform 4) to the 3’-end of PDGFRB. Lissencephaly 10 (LIS10) [MIM:618873] A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS10 is an autosomal dominant form clinically characterized by variably delayed development, mildly to moderately impaired intellectual development, language delay, and seizures. Some patients have normal early development and borderline to mild cognitive impairment. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CEP85 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q5SZL2-1	1	yes
Q5SZL2-2	2
Q5SZL2-3	3
Q5SZL2-4	4
Q5SZL2-5	5

RefSeq proteins (3): NP_001035940, NP_001171506, NP_996804 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040210	Cep85/Cep85L	Family
IPR058190	CC4_CEP85	Domain

Pfam: PF24555

UniProt features (22 total): sequence variant 10, splice variant 4, region of interest 2, modified residue 2, chain 1, coiled-coil region 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SZL2-F1	64.98	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 674–675 (breakpoint for translocation to form the cep85l-pdgfrb fusion protein)

Post-translational modifications (2): 15, 207

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 210 (showing top): GOBP_NEUROGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, FOSTER_TOLERANT_MACROPHAGE_DN, GOCC_CENTROSOME, GOBP_NEURON_MIGRATION, CUI_TCF21_TARGETS_2_DN, VECCHI_GASTRIC_CANCER_EARLY_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOCC_PERICENTRIOLAR_MATERIAL, chr6q22, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, BRUINS_UVC_RESPONSE_LATE, CBX5_TARGET_GENES, GLI1_TARGET_GENES, HES2_TARGET_GENES

GO Biological Process (1): neuron migration (GO:0001764)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): pericentriolar material (GO:0000242), centrosome (GO:0005813), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell migration	1
generation of neurons	1
binding	1
centrosome	1
centriole	1
microtubule organizing center	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

506 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP85L	SLC35F1	Q5T1Q4	602
CEP85L	GOPC	Q9HD26	593
CEP85L	ROS1	P08922	516
CEP85L	ADAMTS2	O95450	473
CEP85L	RET	P07949	467
CEP85L	ADAMTS4	O75173	455
CEP85L	CDK5	Q00535	454
CEP85L	ZCCHC8	Q6NZY4	452
CEP85L	EGFL7	Q9UHF1	451
CEP85L	LRIG3	Q6UXM1	445
CEP85L	KDELR2	P33947	425
CEP85L	CCSAP	Q6IQ19	410
CEP85L	SPICE1	Q8N0Z3	406
CEP85L	SLC34A2	O95436	356
CEP85L	TLCD5	Q6ZRR5	355
CEP85L	TNPO2	O14787	355

IntAct

29 interactions, top by confidence:

A	B	Type	Score
PHKG2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
KLHL40	CBX4	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
TUBA1A	CAPZB	psi-mi:“MI:0914”(association)	0.350
TUBA1A	KIF2A	psi-mi:“MI:0914”(association)	0.350
MARK2	SMAP	psi-mi:“MI:0914”(association)	0.350
rep	STXBP3	psi-mi:“MI:0914”(association)	0.350
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
ACTR2		psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350
CFAP184	TARS3	psi-mi:“MI:0914”(association)	0.350
PIGT	AKAP8	psi-mi:“MI:0914”(association)	0.350
CEP85L	VSIG8	psi-mi:“MI:0914”(association)	0.350
CEP128	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
CNTRL	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
CLU	CEP85L	psi-mi:“MI:0915”(physical association)	0.000
CEP85L	aceF	psi-mi:“MI:0915”(physical association)	0.000
PCNT	CEP85L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): CEP85L (Proximity Label-MS), CEP85L (Proximity Label-MS), CEP85L (Affinity Capture-MS), CEP85L (Affinity Capture-MS), CEP85L (Affinity Capture-MS), CEP85L (Affinity Capture-RNA), CEP85L (Proximity Label-MS), CEP85L (Affinity Capture-RNA), CEP85L (Two-hybrid), TEX11 (Two-hybrid), ZNF417 (Two-hybrid), CEP85L (Proximity Label-MS), CEP85L (Affinity Capture-MS), CEP85L (Affinity Capture-MS), CEP85L (Proximity Label-MS)

ESM2 similar proteins: A0A1L8GUX5, A0A1L8GXY6, A0A1W2P884, A2CE83, B8A5S6, E7F5E1, F7DP49, H2MTR9, O08970, O35711, O60296, P27628, P53564, P60853, Q0VF96, Q28GJ0, Q2KJD6, Q3UIJ9, Q4V7D3, Q5BIX7, Q5R923, Q5SXA9, Q5SZL2, Q5U2Y9, Q5U4W1, Q5ZLT3, Q6AW69, Q6DIS8, Q6DJR2, Q6NRW2, Q6NXJ0, Q6P402, Q6PCQ0, Q6PD31, Q7TQE6, Q80ST9, Q86W92, Q8BMK0, Q8C8U0, Q8CFC9

Diamond homologs: A0A1W2P884, Q5SZL2, Q6P2H3, Q8BMK0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	6	190.3×	2e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	167.9×	2e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	167.9×	2e-11
Activation of BH3-only proteins	6	124.1×	2e-10
RHO GTPases activate PKNs	6	79.3×	2e-09
Intrinsic Pathway for Apoptosis	6	73.2×	3e-09
Translocation of SLC2A4 (GLUT4) to the plasma membrane	9	57.9×	4e-12
SARS-CoV-1-host interactions	6	43.9×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	53.9×	5e-06
intracellular protein localization	7	21.6×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

331 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	9
Uncertain significance	194
Likely benign	63
Benign	19

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1077140	NM_001042475.3(CEP85L):c.232+2T>A	Pathogenic
1320300	NM_001042475.3(CEP85L):c.3G>T (p.Met1Ile)	Pathogenic
1459545	NC_000006.11:g.(?118880085)(118880243_?)del	Pathogenic
180223	NC_000006.11:g.(117810940_117810996)_(119417693_119417749)del	Pathogenic
3062917	GRCh37/hg19 6q22.31(chr6:118786589-119039118)x1	Pathogenic
3365869	NM_001042475.3(CEP85L):c.232+1G>A	Pathogenic
3655536	NM_002667.5(PLN):c.2T>G (p.Met1Arg)	Pathogenic
872889	NM_001042475.3(CEP85L):c.2T>C (p.Met1Thr)	Pathogenic
979037	NM_001042475.3(CEP85L):c.232+1G>T	Pathogenic
980781	GRCh37/hg19 6q22.31(chr6:118871813-119007889)x1	Pathogenic
1120042	NM_001042475.3(CEP85L):c.189T>G (p.Ser63Arg)	Likely pathogenic
1709041	NM_002667.5(PLN):c.63_64del (p.Gln22fs)	Likely pathogenic
3027447	NM_001178035.2(CEP85L):c.57_60del (p.Ser20fs)	Likely pathogenic
3064370	NM_001042475.3(CEP85L):c.2089C>T (p.Gln697Ter)	Likely pathogenic
4291120	NM_001042475.3(CEP85L):c.232+5G>C	Likely pathogenic
872890	NM_001042475.3(CEP85L):c.193G>A (p.Asp65Asn)	Likely pathogenic
979031	NM_001042475.3(CEP85L):c.1A>T (p.Met1Leu)	Likely pathogenic
979032	NM_001042475.3(CEP85L):c.172A>T (p.Ser58Cys)	Likely pathogenic
979036	NM_001042475.3(CEP85L):c.205G>A (p.Gly69Arg)	Likely pathogenic

SpliceAI

2339 predictions. Top by Δscore:

Variant	Effect	Δscore
6:118523800:A:AC	donor_gain	1.0000
6:118523801:C:CC	donor_gain	1.0000
6:118523801:CCGAT:C	donor_gain	1.0000
6:118523867:A:AC	donor_gain	1.0000
6:118523868:C:CC	donor_gain	1.0000
6:118523916:AAAAC:A	acceptor_gain	1.0000
6:118523919:AC:A	acceptor_gain	1.0000
6:118523920:CC:C	acceptor_gain	1.0000
6:118523921:C:CC	acceptor_gain	1.0000
6:118632447:GCTCA:G	donor_loss	1.0000
6:118632448:CTCA:C	donor_loss	1.0000
6:118632449:TCAC:T	donor_loss	1.0000
6:118632450:CAC:C	donor_loss	1.0000
6:118632451:A:AC	donor_gain	1.0000
6:118632451:ACC:A	donor_loss	1.0000
6:118632451:ACCTT:A	donor_gain	1.0000
6:118632452:C:CC	donor_gain	1.0000
6:118632452:CCTTC:C	donor_gain	1.0000
6:118632607:TGGGC:T	acceptor_gain	1.0000
6:118632608:GGGC:G	acceptor_gain	1.0000
6:118632608:GGGCC:G	acceptor_gain	1.0000
6:118632609:GGC:G	acceptor_gain	1.0000
6:118632609:GGCC:G	acceptor_gain	1.0000
6:118632610:GC:G	acceptor_gain	1.0000
6:118632610:GCCT:G	acceptor_gain	1.0000
6:118632611:CC:C	acceptor_gain	1.0000
6:118632611:CCTAA:C	acceptor_gain	1.0000
6:118632612:C:CA	acceptor_loss	1.0000
6:118632612:C:CC	acceptor_gain	1.0000
6:118632612:C:G	acceptor_gain	1.0000

AlphaMissense

5320 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:118483743:A:G	L518P	0.999
6:118483752:A:G	L515P	0.999
6:118483827:A:G	L490P	0.999
6:118469086:A:G	L747S	0.998
6:118483750:C:G	A516P	0.998
6:118511392:A:G	L388P	0.998
6:118469101:G:T	P742H	0.997
6:118483755:T:C	Y514C	0.997
6:118483755:T:G	Y514S	0.997
6:118483756:A:C	Y514D	0.997
6:118483756:A:G	Y514H	0.997
6:118523802:C:G	R380P	0.997
6:118465439:G:T	A795D	0.996
6:118465462:C:A	R787S	0.996
6:118465462:C:G	R787S	0.996
6:118465466:A:G	L786S	0.996
6:118469102:G:A	P742S	0.996
6:118469119:C:G	R736P	0.996
6:118469128:A:G	L733P	0.996
6:118483760:T:A	E512D	0.996
6:118483760:T:G	E512D	0.996
6:118483764:A:G	L511S	0.996
6:118483775:T:A	R507S	0.996
6:118483775:T:G	R507S	0.996
6:118483857:A:G	L480P	0.996
6:118511413:T:G	Q381P	0.996
6:118523829:A:G	L371P	0.996
6:118565654:A:G	W299R	0.996
6:118565654:A:T	W299R	0.996
6:118465487:A:G	L779S	0.995

dbSNP variants (sampled 300 via entrez): RS1000010901 (6:118516843 C>A,T), RS1000014346 (6:118647711 C>T), RS1000026063 (6:118488049 C>A,G,T), RS1000027454 (6:118581871 G>A), RS1000031209 (6:118594300 A>G), RS1000046119 (6:118639065 G>A), RS1000049083 (6:118555808 C>T), RS1000052570 (6:118472785 T>C), RS1000094090 (6:118682988 G>A), RS1000100235 (6:118561617 A>G), RS1000107001 (6:118632879 T>C), RS1000107913 (6:118641047 A>G), RS1000114052 (6:118570815 G>A), RS1000114403 (6:118475400 C>T), RS1000116025 (6:118557151 A>C)

Disease associations

OMIM: gene MIM:618865 | disease phenotypes: MIM:609909, MIM:607432, MIM:618873, MIM:613874, MIM:224700

GenCC curated gene-disease

Disease	Classification	Inheritance
lissencephaly 10	Definitive	Autosomal dominant
lissencephaly due to LIS1 mutation	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
lissencephaly 10	Definitive	AD

Mondo (10): cardiomyopathy (MONDO:0004994), dilated cardiomyopathy 1P (MONDO:0012362), lissencephaly spectrum disorders (MONDO:0018838), lissencephaly 10 (MONDO:0030031), hypertrophic cardiomyopathy 18 (MONDO:0013475), hypertrophic cardiomyopathy (MONDO:0005045), dilated cardiomyopathy (MONDO:0005021), Ebstein anomaly (MONDO:0009144), neurodevelopmental disorder (MONDO:0700092), lissencephaly due to LIS1 mutation (MONDO:0011830)

Orphanet (6): Familial isolated dilated cardiomyopathy (Orphanet:154), Rare cardiomyopathy (Orphanet:167848), Lissencephaly (Orphanet:48471), Rare hypertrophic cardiomyopathy (Orphanet:217569), Dilated cardiomyopathy (Orphanet:217604), Ebstein malformation of the tricuspid valve (Orphanet:1880)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000011	Neurogenic bladder
HP:0000324	Facial asymmetry
HP:0000473	Torticollis
HP:0000486	Strabismus
HP:0000609	Optic nerve hypoplasia
HP:0000668	Hypodontia
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0001249	Intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001302	Pachygyria
HP:0002015	Dysphagia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002197	Generalized-onset seizure
HP:0002353	EEG abnormality
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002384	Focal impaired awareness seizure
HP:0002827	Hip dislocation
HP:0004305	Involuntary movements
HP:0007270	Atypical absence seizure
HP:0007302	Bipolar affective disorder
HP:0007334	Bilateral tonic-clonic seizure with focal onset
HP:0007360	Aplasia/Hypoplasia of the cerebellum
HP:0008765	Auditory hallucination
HP:0008936	Axial hypotonia

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000363_13	QT interval	5.000000e-22
GCST000441_1	Cardiac structure and function	1.000000e-09
GCST000444_2	QT interval	2.000000e-29
GCST000561_8	Electrocardiographic traits	8.000000e-07
GCST001893_3	Electrocardiographic conduction measures	6.000000e-16
GCST003844_31	QRS duration	8.000000e-29
GCST004001_13	Bipolar disorder or attention deficit hyperactivity disorder	6.000000e-08
GCST004001_14	Bipolar disorder or attention deficit hyperactivity disorder	5.000000e-07
GCST004001_2	Bipolar disorder or attention deficit hyperactivity disorder	4.000000e-08
GCST004002_2	Bipolar disorder (age of onset <21) or attention deficit hyperactivity disorder	7.000000e-06
GCST006061_198	Atrial fibrillation	2.000000e-16
GCST007217_4	RR interval (heart rate)	3.000000e-10
GCST007469_5	Rapid automatized naming of digits	2.000000e-06
GCST011010_62	Electrocardiographic traits (multivariate)	1.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004298	cardiovascular measurement
EFO:0005054	QRS complex
EFO:0004831	RR interval
EFO:0005301	reading and spelling ability
EFO:0004327	electrocardiography

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D004437	Ebstein Anomaly	C14.240.400.395; C14.280.400.395; C16.131.240.400.395
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499
D065886	Neurodevelopmental Disorders	F03.625
C563690	Cardiomyopathy, Dilated, 1p (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
trichostatin A	affects cotreatment, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation, affects cotreatment	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT00185250	PHASE2	COMPLETED	Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy
NCT00490347	PHASE2	COMPLETED	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Feasibility Trial
NCT00694161	PHASE2	COMPLETED	The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy