EML1

Summary

EML1 (EMAP like 1, HGNC:3330) is a protein-coding gene on chromosome 14q32.2, encoding Echinoderm microtubule-associated protein-like 1 (O00423). Modulates the assembly and organization of the microtubule cytoskeleton, and probably plays a role in regulating the orientation of the mitotic spindle and the orientation of the plane of cell division.

Human echinoderm microtubule-associated protein-like is a strong candidate for the Usher syndrome type 1A gene. Usher syndromes (USHs) are a group of genetic disorders consisting of congenital deafness, retinitis pigmentosa, and vestibular dysfunction of variable onset and severity depending on the genetic type. The disease process in USHs involves the entire brain and is not limited to the posterior fossa or auditory and visual systems. The USHs are catagorized as type I (USH1A, USH1B, USH1C, USH1D, USH1E and USH1F), type II (USH2A and USH2B) and type III (USH3). The type I is the most severe form. Gene loci responsible for these three types are all mapped. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2009 — RefSeq curated summary.

At a glance

• Gene–disease (curated): band heterotopia of brain (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 254 total — 8 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_004434

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3330
Approved symbol	EML1
Name	EMAP like 1
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	EMAP, HuEMAP, ELP79
Ensembl gene	ENSG00000066629
Ensembl biotype	protein_coding
OMIM	602033
Entrez	2009

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 22 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000262233, ENST00000327921, ENST00000334192, ENST00000553313, ENST00000553720, ENST00000554111, ENST00000554386, ENST00000554479, ENST00000554553, ENST00000555096, ENST00000555145, ENST00000555277, ENST00000555812, ENST00000556199, ENST00000556714, ENST00000556758, ENST00000556835, ENST00000556947, ENST00000557313, ENST00000557741, ENST00000649352, ENST00000697131, ENST00000909078, ENST00000909079, ENST00000909080, ENST00000909081, ENST00000909082, ENST00000912116, ENST00000940979, ENST00000940980

RefSeq mRNA: 4 — MANE Select: NM_004434 NM_001008707, NM_001375411, NM_001375412, NM_004434

CCDS: CCDS32154, CCDS32155

Canonical transcript exons

ENST00000262233 — 22 exons

Exon	Start	End
ENSE00000941475	99894629	99894758
ENSE00000941483	99914566	99914697
ENSE00000941484	99917782	99917849
ENSE00000996488	99891199	99891227
ENSE00001363583	99939987	99942060
ENSE00003477678	99850853	99851035
ENSE00003495008	99897145	99897294
ENSE00003516992	99898233	99898302
ENSE00003527445	99920789	99920877
ENSE00003542521	99865514	99865646
ENSE00003552650	99939197	99939327
ENSE00003567470	99878485	99878619
ENSE00003586412	99936029	99936126
ENSE00003621546	99910242	99910341
ENSE00003621758	99937817	99937912
ENSE00003638434	99936247	99936334
ENSE00003638764	99907638	99907733
ENSE00003639118	99914179	99914304
ENSE00003673485	99911422	99911576
ENSE00003685072	99909345	99909479
ENSE00003686835	99900929	99901039
ENSE00003900021	99793413	99793543

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.8567 / max 217.5538, expressed in 1410 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141404	5.8963	1306
141403	2.3646	1063
141398	1.3523	466
141402	0.7214	445
141401	0.2644	115
141400	0.1798	52
141399	0.0780	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.51	gold quality
ganglionic eminence	UBERON:0004023	95.60	gold quality
mucosa of stomach	UBERON:0001199	94.67	gold quality
synovial joint	UBERON:0002217	94.29	gold quality
colonic epithelium	UBERON:0000397	93.00	gold quality
ventricular zone	UBERON:0003053	92.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.25	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.77	gold quality
calcaneal tendon	UBERON:0003701	91.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.50	gold quality
lower esophagus	UBERON:0013473	91.45	gold quality
endometrium epithelium	UBERON:0004811	90.76	gold quality
tendon	UBERON:0000043	90.50	gold quality
right lung	UBERON:0002167	90.46	gold quality
amniotic fluid	UBERON:0000173	90.38	gold quality
stromal cell of endometrium	CL:0002255	90.26	gold quality
tendon of biceps brachii	UBERON:0008188	90.08	gold quality
sural nerve	UBERON:0015488	89.59	gold quality
gall bladder	UBERON:0002110	89.05	gold quality
middle frontal gyrus	UBERON:0002702	88.45	gold quality
frontal pole	UBERON:0002795	88.43	gold quality
bronchial epithelial cell	CL:0002328	88.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.84	gold quality
corpus callosum	UBERON:0002336	87.67	gold quality
descending thoracic aorta	UBERON:0002345	87.20	gold quality
right coronary artery	UBERON:0001625	86.77	gold quality
caudate nucleus	UBERON:0001873	86.68	gold quality
pigmented layer of retina	UBERON:0001782	86.59	gold quality
retina	UBERON:0000966	86.58	gold quality
apex of heart	UBERON:0002098	86.52	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	29.20
E-ANND-3	yes	10.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting EML1, 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-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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6873-3P	100.00	71.42	2626
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-548C-3P	99.99	74.01	7587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-101-3P	99.94	75.03	2230

Literature-anchored findings (GeneRIF, showing 8)

• determined a 2.6-A crystal structure of the representative approximately 70-kDa core of EML1, revealing an intimately associated pair of beta-propellers, which we term a TAPE (tandem atypical propeller in EMLs) domain (PMID:24706829)
• We found EML1 to be mutated in ribbon-like heterotopia in humans (PMID:24859200)
• We show that the trimerization domain (TD) of EML1 is necessary and sufficient for self-association. The TD is also essential for MT binding; however, this property requires an adjacent basic region. (PMID:25740311)
• a homozygous truncating variant in EML1 is a novel cause of congenital hydrocephalus. (PMID:28556411)
• Mutations in the Heterotopia Gene Eml1/EML1 Severely Disrupt the Formation of Primary Cilia. (PMID:31390572)
• biallelic EML1 disease-causing variants cause a highly specific pattern of congenital brain malformations, severe developmental delay, seizures and visual impairment (PMID:31710781)
• A novel missense variant in the EML1 gene associated with bilateral ribbon-like subcortical heterotopia leads to ciliary defects. (PMID:34211111)
• Human cerebral organoids reveal progenitor pathology in EML1-linked cortical malformation. (PMID:35289477)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	eml1	ENSDARG00000042840
mus_musculus	Eml1	ENSMUSG00000058070
rattus_norvegicus	Eml1	ENSRNOG00000043143

Paralogs (9): EML2 (ENSG00000125746), EML4 (ENSG00000143924), EML3 (ENSG00000149499), CFAP251 (ENSG00000158023), WDR90 (ENSG00000161996), EML5 (ENSG00000165521), CFAP52 (ENSG00000166596), CFAP44 (ENSG00000206530), EML6 (ENSG00000214595)

Protein

Protein identifiers

Echinoderm microtubule-associated protein-like 1 — O00423 (reviewed: O00423)

All UniProt accessions (16): O00423, A0A3B3IU69, A0A8V8TKR4, F8W717, G3V3J1, G3V3N9, G3V497, G3V4H6, G3V4U5, G3V500, G3V538, G3V5C8, H0YJD8, H0YJK4, H0YJS9, H0YJY3

UniProt curated annotations — full annotation on UniProt →

Function. Modulates the assembly and organization of the microtubule cytoskeleton, and probably plays a role in regulating the orientation of the mitotic spindle and the orientation of the plane of cell division. Required for normal proliferation of neuronal progenitor cells in the developing brain and for normal brain development. Does not affect neuron migration per se.

Subunit / interactions. Homotrimer; self-association is mediated by the N-terminal coiled coil. Does not interact with EML3. Binds repolymerizing microtubules. Binds unpolymerized tubulins via its WD repeat region. Interacts with TASOR.

Subcellular location. Cytoplasm. Perinuclear region. Cytoskeleton.

Tissue specificity. Ubiquitous; expressed in most tissues with the exception of thymus and peripheral blood lymphocytes.

Disease relevance. Band heterotopia (BH) [MIM:600348] A brain malformation of the lissencephaly spectrum, resulting from disordered neuronal migration and characterized by bands of gray matter interposed in the central white matter. Disease features include severe developmental delay with intellectual disability, enlarged head circumference, periventricular and ribbon-like subcortical heterotopia, polymicrogyria and agenesis of the corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Contains a tandem atypical propeller in EMLs (TAPE) domain. The N-terminal beta-propeller is formed by canonical WD repeats; in contrast, the second beta-propeller contains one blade that is formed by discontinuous parts of the polypeptide chain. The N-terminal coiled coil is required for association with microtubules.

Similarity. Belongs to the WD repeat EMAP family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00423-1	1	yes
O00423-3	3

RefSeq proteins (4): NP_001008707, NP_001362340, NP_001362341, NP_004425* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR005108	HELP	Conserved_site
IPR011047	Quinoprotein_ADH-like_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050630	WD_repeat_EMAP	Family
IPR055439	Beta-prop_EML_1st	Domain
IPR055442	Beta-prop_EML-like_2nd	Domain

Pfam: PF03451, PF23409, PF23414

UniProt features (115 total): strand 58, repeat 12, turn 10, mutagenesis site 8, sequence conflict 7, sequence variant 6, helix 4, compositionally biased region 4, region of interest 2, chain 1, coiled-coil region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4CI8	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00423-F1	86.49	0.76

Functional residue map

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

Post-translational modifications (1): 113

Mutagenesis-validated functional residues (8):

Position	Phenotype
59–61	no effect on tubulin binding. does not disrupt self-association. decreased association with microtubules.
192	abolishes tubulin binding; when associated with s-194; a-547; t-626; s-627; a-646 and a-786.
194	abolishes tubulin binding; when associated with s-192; a-547; t-626; s-627; a-646 and a-786.
547	abolishes tubulin binding; when associated with s-192; s-194; t-626; s-627; a-646 and a-786.
626	abolishes tubulin binding; when associated with s-192; s-194; a-547; s-627; a-646 and a-786.
627	abolishes tubulin binding; when associated with s-192; s-194; a-547; t-626; a-646 and a-786.
646	abolishes tubulin binding; when associated with s-192; s-194; a-547; t-626; s-627 and a-786.
786	abolishes tubulin binding; when associated with s-192; s-194; a-547; t-626; s-627 and a-646.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 190 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, FOXO1_01, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, PAX8_B, MYOD_01, DELYS_THYROID_CANCER_DN, MODULE_99, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, ONDER_CDH1_TARGETS_2_UP, GOBP_MITOTIC_CELL_CYCLE, HTF_01, HIF1_Q3, GOBP_HEAD_DEVELOPMENT, RFX1_02

GO Biological Process (5): microtubule cytoskeleton organization (GO:0000226), hematopoietic progenitor cell differentiation (GO:0002244), mitotic spindle organization (GO:0007052), neuroblast proliferation (GO:0007405), brain development (GO:0007420)

GO Molecular Function (4): calcium ion binding (GO:0005509), microtubule binding (GO:0008017), tubulin binding (GO:0015631), protein binding (GO:0005515)

GO Cellular Component (10): cytosol (GO:0005829), microtubule (GO:0005874), microtubule associated complex (GO:0005875), perinuclear region of cytoplasm (GO:0048471), mitotic spindle pole (GO:0097431), mitotic spindle midzone (GO:1990023), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630), mitotic spindle (GO:0072686)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
microtubule cytoskeleton	2
mitotic spindle	2
cytoskeleton organization	1
microtubule-based process	1
hemopoiesis	1
cell differentiation	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
generation of neurons	1
neural precursor cell proliferation	1
central nervous system development	1
animal organ development	1
head development	1
metal ion binding	1
tubulin binding	1
cytoskeletal protein binding	1
binding	1
polymeric cytoskeletal fiber	1
protein-containing complex	1
spindle pole	1
spindle midzone	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cytoskeleton	1
spindle	1

Protein interactions and networks

STRING

1873 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EML1	ALK	Q9UM73	739
EML1	NUP214	P35658	545
EML1	KIF2A	O00139	492
EML1	EGFR	P00533	471
EML1	TMEM91	Q6ZNR0	453
EML1	OR52E2	Q8NGJ4	450
EML1	ANKRD13B	Q86YJ7	450
EML1	KIAA0513	O60268	449
EML1	ERMARD	Q5T6L9	448
EML1	RCSD1	Q6JBY9	447
EML1	TMEM25	Q86YD3	440
EML1	ETV6	P41212	404
EML1	KIF13A	Q9H1H9	398
EML1	KIF5A	Q12840	398
EML1	ARFGEF2	Q9Y6D5	396

IntAct

34 interactions, top by confidence:

A	B	Type	Score
EML1	ISG20L2	psi-mi:“MI:0915”(physical association)	0.620
EML1	CASP6	psi-mi:“MI:0915”(physical association)	0.560
EML1	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
EML1	STIP1	psi-mi:“MI:0915”(physical association)	0.560
NUDC	EML1	psi-mi:“MI:0915”(physical association)	0.560
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
EML1	FXR1	psi-mi:“MI:0915”(physical association)	0.510
EML1	PTEN	psi-mi:“MI:0915”(physical association)	0.370
EML1	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
EML1	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	EML1	psi-mi:“MI:0915”(physical association)	0.370
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
TUBB3	TUBB8B	psi-mi:“MI:0914”(association)	0.350
EML1	TUBB	psi-mi:“MI:0914”(association)	0.350
TUBB2B	POTEF	psi-mi:“MI:0914”(association)	0.350
FBXO28	EML1	psi-mi:“MI:0914”(association)	0.350
EML1	EML2	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): EML1 (Affinity Capture-MS), EML1 (Affinity Capture-MS), ISG20L2 (Two-hybrid), EML1 (Proximity Label-MS), EML1 (Affinity Capture-MS), EML1 (Affinity Capture-Western), TUBA1A (Reconstituted Complex), TUBB3 (Reconstituted Complex), FBXO28 (Affinity Capture-MS), TUBB2A (Affinity Capture-MS), EML4 (Affinity Capture-MS), TUBB2B (Affinity Capture-MS), EML1 (Affinity Capture-MS), TUBB (Affinity Capture-MS), EML1 (Proximity Label-MS)

ESM2 similar proteins: A0A396ISC0, O00423, O13286, O17468, O61585, O94423, P26309, P38328, P43254, P53197, P78972, P93471, Q04199, Q05BC3, Q09373, Q12834, Q16MY0, Q2TAF3, Q32SG6, Q3E906, Q4PSE4, Q4V7Y7, Q4V8C3, Q54MZ3, Q5H7C0, Q5ZIU8, Q62623, Q652L2, Q6DIP5, Q6NVM2, Q6S7B0, Q7K0L4, Q7ZUV2, Q7ZVL2, Q7ZX22, Q86Y33, Q8BG40, Q8CFJ9, Q8L3Z8, Q8LPL5

Diamond homologs: O00423, O95834, Q05BC3, Q05BV3, Q26613, Q2TAF3, Q32P44, Q3UMY5, Q4V8C3, Q5SQM0, Q6DIP5, Q6ED65, Q6P6T4, Q6ZMW3, Q7TNG5, Q8BQM8, Q8VC03, Q9HC35, Q9N9X3, Q9VUI3, Q9Y1C1, B3MC74, B4JW81, B4KTK4, B4LJT7, B4MY77, P29829, Q9NFZ1, B6K1G6, O48847, Q15542, Q8C092, O22212, O45487, O75083, O88342, O93277, Q2KJH4, Q5RKI0, Q86HX1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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
Selective autophagy	5	66.3×	5e-07
Aggrephagy	5	59.1×	7e-07
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	55.3×	1e-07
Recycling pathway of L1	5	53.3×	1e-06
COPI-independent Golgi-to-ER retrograde traffic	5	49.4×	1e-06
Kinesins	5	42.5×	1e-06
Autophagy	6	42.4×	3e-07
Golgi-to-ER retrograde transport	5	31.6×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
microtubule cytoskeleton organization	6	30.3×	1e-05
mitotic cell cycle	5	27.9×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	3
Uncertain significance	106
Likely benign	74
Benign	52

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1031421	NM_004434.3(EML1):c.1820+1G>C	Pathogenic
2133786	NM_004434.3(EML1):c.1715_1735delinsAGAC (p.Ala572fs)	Pathogenic
254258	NM_004434.3(EML1):c.412C>T (p.Arg138Ter)	Pathogenic
254260	NM_004434.3(EML1):c.673T>C (p.Trp225Arg)	Pathogenic
2754922	NM_004434.3(EML1):c.753_765del (p.Ser252fs)	Pathogenic
4796662	NM_004434.3(EML1):c.547+1G>T	Pathogenic
548146	NM_004434.3(EML1):c.1567C>T (p.Arg523Ter)	Pathogenic
813332	GRCh37/hg19 14q32.2(chr14:100317190-101012999)	Pathogenic
1028240	NM_004434.3(EML1):c.1897C>T (p.Arg633Ter)	Likely pathogenic
1710368	NM_004434.3(EML1):c.136C>T (p.Gln46Ter)	Likely pathogenic
254259	NM_004434.3(EML1):c.727A>G (p.Thr243Ala)	Likely pathogenic

SpliceAI

4275 predictions. Top by Δscore:

Variant	Effect	Δscore
14:99793505:GCCT:G	donor_gain	1.0000
14:99850845:T:TA	acceptor_gain	1.0000
14:99850850:TAG:T	acceptor_gain	1.0000
14:99850851:A:AG	acceptor_gain	1.0000
14:99850851:AG:A	acceptor_loss	1.0000
14:99850851:AGA:A	acceptor_gain	1.0000
14:99850852:G:GT	acceptor_gain	1.0000
14:99850852:GAT:G	acceptor_gain	1.0000
14:99851019:G:GT	donor_gain	1.0000
14:99851020:A:T	donor_gain	1.0000
14:99851031:CAAAG:C	donor_loss	1.0000
14:99851032:AAAG:A	donor_loss	1.0000
14:99851033:AAGG:A	donor_loss	1.0000
14:99851036:GT:G	donor_loss	1.0000
14:99851037:T:A	donor_loss	1.0000
14:99865508:TTACA:T	acceptor_loss	1.0000
14:99865510:ACAG:A	acceptor_loss	1.0000
14:99865511:CAG:C	acceptor_loss	1.0000
14:99865512:A:AG	acceptor_gain	1.0000
14:99865513:G:A	acceptor_loss	1.0000
14:99865513:G:GA	acceptor_gain	1.0000
14:99865513:GC:G	acceptor_gain	1.0000
14:99865513:GCA:G	acceptor_gain	1.0000
14:99865513:GCAA:G	acceptor_gain	1.0000
14:99865642:AAAAG:A	donor_loss	1.0000
14:99865644:AAGG:A	donor_loss	1.0000
14:99865645:AGG:A	donor_loss	1.0000
14:99865646:GGT:G	donor_loss	1.0000
14:99865647:G:GA	donor_loss	1.0000
14:99865648:T:A	donor_loss	1.0000

AlphaMissense

5338 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:99850949:T:C	L55P	1.000
14:99850961:T:C	L59P	1.000
14:99900953:T:A	W308R	1.000
14:99900953:T:C	W308R	1.000
14:99909412:G:A	G391E	1.000
14:99909432:T:A	W398R	1.000
14:99909432:T:C	W398R	1.000
14:99910332:T:A	W444R	1.000
14:99910332:T:C	W444R	1.000
14:99920790:T:A	W608R	1.000
14:99920790:T:C	W608R	1.000
14:99936050:G:A	G644D	1.000
14:99936256:A:C	S673R	1.000
14:99936257:G:T	S673I	1.000
14:99936258:C:A	S673R	1.000
14:99936258:C:G	S673R	1.000
14:99936259:T:C	F674L	1.000
14:99936261:C:A	F674L	1.000
14:99936261:C:G	F674L	1.000
14:99936277:T:A	W680R	1.000
14:99936277:T:C	W680R	1.000
14:99936304:T:C	S689P	1.000
14:99936310:T:C	S691P	1.000
14:99936311:C:T	S691F	1.000
14:99939281:A:C	D759A	1.000
14:99939281:A:T	D759V	1.000
14:99940024:T:A	V787D	1.000
14:99940098:T:A	W812R	1.000
14:99940098:T:C	W812R	1.000
14:99850907:T:C	L41P	0.999

dbSNP variants (sampled 300 via entrez): RS1000008963 (14:99813975 G>A), RS1000027117 (14:99809326 G>T), RS1000057326 (14:99740719 G>A), RS1000059448 (14:99822555 G>A,T), RS1000076282 (14:99767646 G>A), RS1000139251 (14:99800190 A>G), RS1000143595 (14:99864129 A>G,T), RS1000154140 (14:99908102 G>A), RS1000164980 (14:99768981 G>C,T), RS1000171760 (14:99860543 C>G,T), RS1000195676 (14:99744228 C>T), RS1000209788 (14:99738464 C>A), RS1000238200 (14:99887862 C>G), RS1000238933 (14:99910899 C>A,T), RS1000255581 (14:99799959 A>G)

Disease associations

OMIM: gene MIM:602033 | disease phenotypes: MIM:600348, MIM:617557

GenCC curated gene-disease

Disease	Classification	Inheritance
band heterotopia of brain	Strong	Autosomal recessive
subcortical band heterotopia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
band heterotopia of brain	Definitive	AR

Mondo (3): band heterotopia of brain (MONDO:0010873), Gabriele de Vries syndrome (MONDO:0044738), subcortical band heterotopia (MONDO:0020491)

Orphanet (1): Gabriele-de Vries syndrome (Orphanet:506358)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000708	Atypical behavior
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001357	Plagiocephaly
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002282	Gray matter heterotopia
HP:0002360	Sleep disturbance
HP:0003577	Congenital onset
HP:0006956	Lateral ventricle dilatation
HP:0010864	Severe intellectual disability
HP:0012736	Profound global developmental delay
HP:0025517	Hypoplastic hippocampus
HP:0032409	Subcortical band heterotopia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003474_8	Scalp hair shape	1.000000e-07
GCST005194_177	Coronary artery disease	4.000000e-08
GCST006427_27	Depression in smokers	1.000000e-06
GCST007096_151	Pulse pressure	7.000000e-10
GCST007097_162	Pulse pressure	2.000000e-06
GCST007097_163	Pulse pressure	3.000000e-08
GCST008473_1	Visceral fat	3.000000e-06
GCST010703_106	Brain morphology (MOSTest)	1.000000e-20
GCST90000025_550	Appendicular lean mass	2.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563950	Band Heterotopia of Brain (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression	3
sodium arsenite	decreases expression, increases expression	2
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	2
Acrolein	increases abundance, affects cotreatment, decreases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance, increases expression	2
Aflatoxin B1	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	increases expression	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_ZD03	Mel 04.01	Cancer cell line	Male
CVCL_ZD06	Mel 12.07	Cancer cell line	Male

Clinical trials (associated diseases)

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