EPB41L1

Summary

EPB41L1 (erythrocyte membrane protein band 4.1 like 1, HGNC:3378) is a protein-coding gene on chromosome 20q11.23, encoding Band 4.1-like protein 1 (Q9H4G0). May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases.

Erythrocyte membrane protein band 4.1 (EPB41) is a multifunctional protein that mediates interactions between the erythrocyte cytoskeleton and the overlying plasma membrane. The encoded protein binds and stabilizes D2 and D3 dopamine receptors at the neuronal plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2036 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant non-syndromic intellectual disability (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 212 total — 1 likely-pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_012156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3378
Approved symbol	EPB41L1
Name	erythrocyte membrane protein band 4.1 like 1
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0338, 4.1N
Ensembl gene	ENSG00000088367
Ensembl biotype	protein_coding
OMIM	602879
Entrez	2036

Gene structure

Transcript identifiers

Ensembl transcripts: 99 — 98 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000202028, ENST00000338074, ENST00000373941, ENST00000373945, ENST00000373946, ENST00000373950, ENST00000406771, ENST00000427533, ENST00000430276, ENST00000432589, ENST00000432603, ENST00000441639, ENST00000447825, ENST00000451082, ENST00000452261, ENST00000454226, ENST00000479336, ENST00000628415, ENST00000636016, ENST00000887203, ENST00000887204, ENST00000887205, ENST00000887206, ENST00000887207, ENST00000887208, ENST00000887209, ENST00000887210, ENST00000887211, ENST00000887212, ENST00000887213, ENST00000887214, ENST00000887215, ENST00000887216, ENST00000887217, ENST00000887218, ENST00000887219, ENST00000887220, ENST00000887221, ENST00000887222, ENST00000887223, ENST00000887224, ENST00000887225, ENST00000887226, ENST00000887227, ENST00000887228, ENST00000887229, ENST00000887230, ENST00000887231, ENST00000887232, ENST00000887233, ENST00000887234, ENST00000887235, ENST00000887236, ENST00000887237, ENST00000887238, ENST00000887239, ENST00000887240, ENST00000887241, ENST00000887242, ENST00000887243, ENST00000887244, ENST00000887245, ENST00000887246, ENST00000887247, ENST00000887248, ENST00000887249, ENST00000887250, ENST00000887251, ENST00000887252, ENST00000887253, ENST00000887254, ENST00000887255, ENST00000887256, ENST00000887257, ENST00000887258, ENST00000887259, ENST00000887260, ENST00000887261, ENST00000887262, ENST00000887263, ENST00000887264, ENST00000887265, ENST00000887266, ENST00000887267, ENST00000887268, ENST00000887269, ENST00000887270, ENST00000912860, ENST00000912861, ENST00000912862, ENST00000912863, ENST00000912864, ENST00000912865, ENST00000941883, ENST00000941884, ENST00000941885, ENST00000941886, ENST00000941887, ENST00000941888

RefSeq mRNA: 40 — MANE Select: NM_012156 NM_001258329, NM_001258330, NM_001258331, NM_001424373, NM_001424374, NM_001424375, NM_001424376, NM_001424377, NM_001424378, NM_001424379, NM_001424380, NM_001424381, NM_001424382, NM_001424383, NM_001424384, NM_001424385, NM_001424386, NM_001424387, NM_001424388, NM_001424389, NM_001424390, NM_001424391, NM_001424392, NM_001424393, NM_001424394, NM_001424395, NM_001424396, NM_001424397, NM_001424398, NM_001424399, NM_001424400, NM_001424401, NM_001424402, NM_001424403, NM_001424404, NM_001424405, NM_001424406, NM_001424407, NM_012156, NM_177996

CCDS: CCDS13271, CCDS13272, CCDS58770, CCDS58771

Canonical transcript exons

ENST00000338074 — 22 exons

Exon	Start	End
ENSE00001605763	36190622	36190797
ENSE00001615181	36194212	36194360
ENSE00001629817	36214357	36214440
ENSE00001640311	36229332	36232799
ENSE00001677409	36222278	36222394
ENSE00001699891	36188347	36188499
ENSE00001705630	36187676	36187763
ENSE00001710295	36195329	36195364
ENSE00001720724	36218876	36218962
ENSE00001753266	36197859	36198041
ENSE00001768994	36178630	36178672
ENSE00001772042	36190277	36190374
ENSE00001783625	36219761	36219844
ENSE00001804873	36177952	36178056
ENSE00001939062	36154740	36154896
ENSE00003476905	36209488	36209898
ENSE00003682871	36212272	36212376
ENSE00003786302	36182272	36182347
ENSE00003786448	36175551	36175715
ENSE00003787834	36221864	36221944
ENSE00003788206	36185117	36185335
ENSE00003794415	36173764	36173954

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.5625 / max 285.2699, expressed in 1589 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184357	6.2298	959
184368	4.1083	631
184367	3.4563	1200
184355	1.6578	578
184364	1.2853	365
184366	0.9258	538
184350	0.7837	265
184353	0.6951	347
184365	0.3334	149
184354	0.2896	160

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior vestibular nucleus	UBERON:0007227	98.63	gold quality
substantia nigra pars compacta	UBERON:0001965	98.38	gold quality
adrenal tissue	UBERON:0018303	98.34	gold quality
pons	UBERON:0000988	98.28	gold quality
lateral globus pallidus	UBERON:0002476	98.12	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.10	gold quality
medulla oblongata	UBERON:0001896	97.97	gold quality
parietal lobe	UBERON:0001872	97.77	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.74	gold quality
ventral tegmental area	UBERON:0002691	97.69	gold quality
postcentral gyrus	UBERON:0002581	97.68	gold quality
middle temporal gyrus	UBERON:0002771	97.50	gold quality
right adrenal gland	UBERON:0001233	97.48	gold quality
right adrenal gland cortex	UBERON:0035827	97.48	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.40	gold quality
medial globus pallidus	UBERON:0002477	97.39	gold quality
left adrenal gland	UBERON:0001234	97.35	gold quality
prefrontal cortex	UBERON:0000451	97.34	gold quality
globus pallidus	UBERON:0001875	97.33	gold quality
superior frontal gyrus	UBERON:0002661	97.33	gold quality
adrenal cortex	UBERON:0001235	97.21	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.19	gold quality
adrenal gland	UBERON:0002369	97.17	gold quality
left adrenal gland cortex	UBERON:0035825	97.15	gold quality
frontal cortex	UBERON:0001870	97.09	gold quality
occipital lobe	UBERON:0002021	97.09	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.09	gold quality
frontal lobe	UBERON:0016525	97.09	gold quality
inferior vagus X ganglion	UBERON:0005363	97.04	gold quality
primary visual cortex	UBERON:0002436	96.98	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	28.41
E-ANND-3	yes	11.33
E-GEOD-84465	yes	6.94
E-CURD-85	no	193.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

192 targeting EPB41L1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-9902	99.89	69.15	2250

Literature-anchored findings (GeneRIF, showing 8)

• protein 4.1N/dopamine receptor interaction is required for localization or stability of dopamine receptors at the neuronal plasma membrane. (PMID:12181426)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• Kainate receptor GluK2a post-translational modifications differentially regulate association with 4.1N to control activity-dependent receptor endocytosis (PMID:23400781)
• Data suggest that repression of JNK-c-Jun signaling through pancreatic polypeptide receptor 1 (PP1) is one of the key anti-tumor mechanisms of neuronal membrane cytoskeletal protein 4.1 (4.1N). (PMID:26575790)
• the data of the current study identified 4.1N as an inhibitor of hypoxiainduced tumor progression in epithelial ovarian cancer cells. (PMID:26648170)
• Data show that overexpression of 4.1N protein decreased expression of flotillin-1, decreased activation of beta-catenin/Wnt pathway in non-small-cell lung cancer (NSCLC) cells. (PMID:27448302)
• 4.1N, betaII spectrin and ankyrin G are structural components of the lateral membrane skeleton and this skeleton plays an essential role in the assembly of a fully functional lateral membrane. (PMID:29428502)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Epb41l1	ENSMUSG00000027624
rattus_norvegicus	Epb41l1	ENSRNOG00000057817
drosophila_melanogaster	yrt	FBGN0004049
drosophila_melanogaster	cora	FBGN0010434
drosophila_melanogaster	Frmd5	FBGN0032225
caenorhabditis_elegans	erm-1	WBGENE00001333
caenorhabditis_elegans	frm-1	WBGENE00001488
caenorhabditis_elegans		WBGENE00001489
caenorhabditis_elegans	frm-4	WBGENE00001491

Paralogs (10): MYLIP (ENSG00000007944), EPB41L2 (ENSG00000079819), EPB41L3 (ENSG00000082397), EPB41L4B (ENSG00000095203), EPB41L5 (ENSG00000115109), EPB41L4A (ENSG00000129595), FRMD6 (ENSG00000139926), EPB41 (ENSG00000159023), FRMD5 (ENSG00000171877), FRMD3 (ENSG00000172159)

Protein

Protein identifiers

Band 4.1-like protein 1 — Q9H4G0 (reviewed: Q9H4G0)

Alternative names: Erythrocyte membrane protein band 4.1-like 1, Neuronal protein 4.1

All UniProt accessions (13): Q9H4G0, A0A0C4DH22, A0A1B0GTW6, H0Y482, H7C2K6, Q4VXN0, Q4VXN1, Q4VXN2, Q4VXN5, Q4VXN6, Q4VXN7, Q4VXN8, X6RC15

UniProt curated annotations — full annotation on UniProt →

Function. May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases.

Subunit / interactions. Interacts with AGAP2.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Highest expression in brain, lower in heart, kidney, pancreas, placenta, lung and skeletal muscle.

Disease relevance. Intellectual developmental disorder, autosomal dominant 11 (MRD11) [MIM:614257] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H4G0-1	1	yes
Q9H4G0-2	2
Q9H4G0-3	3
Q9H4G0-4	4

RefSeq proteins (40): NP_001245258, NP_001245259, NP_001245260, NP_001411302, NP_001411303, NP_001411304, NP_001411305, NP_001411306, NP_001411307, NP_001411308, NP_001411309, NP_001411310, NP_001411311, NP_001411312, NP_001411313, NP_001411314, NP_001411315, NP_001411316, NP_001411317, NP_001411318, NP_001411319, NP_001411320, NP_001411321, NP_001411322, NP_001411323, NP_001411324, NP_001411325, NP_001411326, NP_001411327, NP_001411328, NP_001411329, NP_001411330, NP_001411331, NP_001411332, NP_001411333, NP_001411334, NP_001411335, NP_001411336, NP_036288, NP_818932 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000798	Ez/rad/moesin-like	Family
IPR007477	SAB_dom	Domain
IPR008379	Band_4.1_C	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR014847	FA	Domain
IPR018979	FERM_N	Domain
IPR018980	FERM_PH-like_C	Domain
IPR019747	FERM_CS	Conserved_site
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily

Pfam: PF00373, PF04382, PF05902, PF08736, PF09379, PF09380

UniProt features (55 total): modified residue 32, compositionally biased region 7, region of interest 6, splice variant 6, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4G0-F1	62.40	0.32

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 (32): 30, 75, 79, 343, 378, 430, 437, 461, 466, 475, 510, 540, 541, 544, 546, 550, 564, 578, 580, 639 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-6794361	Neurexins and neuroligins
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea

MSigDB gene sets: 244 (showing top): GCACCTT_MIR18A_MIR18B, KOBAYASHI_EGFR_SIGNALING_24HR_UP, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, KEGG_TIGHT_JUNCTION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, AP1_Q4_01, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, ATTACAT_MIR3803P, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, TGANTCA_AP1_C, NRF2_Q4, RYTTCCTG_ETS2_B, GOMF_ACTIN_BINDING

GO Biological Process (2): cortical actin cytoskeleton organization (GO:0030866), actomyosin structure organization (GO:0031032)

GO Molecular Function (4): actin binding (GO:0003779), structural molecule activity (GO:0005198), protein binding (GO:0005515), cytoskeletal protein binding (GO:0008092)

GO Cellular Component (4): cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sensory processing of sound	2
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1
Protein-protein interactions at synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin cytoskeleton organization	2
cellular anatomical structure	2
cortical cytoskeleton organization	1
cytoskeletal protein binding	1
molecular_function	1
binding	1
protein binding	1
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1144 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPB41L1	GRIA1	P42261	991
EPB41L1	HOMER1	Q86YM7	740
EPB41L1	AGAP2	Q99490	715
EPB41L1	DLG1	Q12959	698
EPB41L1	PICK1	Q9NRD5	677
EPB41L1	ANK3	Q12955	655
EPB41L1	LGMN	Q99538	647
EPB41L1	DLG4	P78352	645
EPB41L1	GRIK2	Q13002	640
EPB41L1	ANK2	Q01484	610
EPB41L1	ANK1	P16157	597
EPB41L1	SSTR4	P31391	588
EPB41L1	SLC32A1	Q9H598	557
EPB41L1	SPTBN1	Q01082	550
EPB41L1	NETO2	Q8NC67	536

IntAct

81 interactions, top by confidence:

A	B	Type	Score
PEA15	MAPK1	psi-mi:“MI:0914”(association)	0.900
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
DDAH2	EPB41L2	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	SIAH2	psi-mi:“MI:0914”(association)	0.530
MISP	OBSL1	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	TNRC18	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	TUBG1	psi-mi:“MI:0914”(association)	0.530
DDAH2	OGT	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	METTL18	psi-mi:“MI:0914”(association)	0.530
LYZL6	COL6A1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	TERF1	psi-mi:“MI:0915”(physical association)	0.510
EPB41L1	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
POT1	EPB41L1	psi-mi:“MI:0915”(physical association)	0.370
EPB41L1	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
EPB41L1	STARD13	psi-mi:“MI:0915”(physical association)	0.370
SPG11	EPB41L1	psi-mi:“MI:0915”(physical association)	0.370
EPB41L1	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
EPB41L1	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
EPB41L1	PPP1CC	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (212): NUMA1 (Two-hybrid), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Two-hybrid), EPB41L1 (Proximity Label-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), EPB41L1 (Proximity Label-MS)

ESM2 similar proteins: A0A0U1QT59, A2VEY9, A8X9H4, D3KZG3, O35412, O35607, O57474, O61366, O93383, P18861, P29415, P34535, P36383, P43322, P49414, P50605, P60571, P91682, Q02297, Q03345, Q05199, Q11069, Q13873, Q14693, Q2THW7, Q2THW9, Q2THX1, Q5R838, Q5RJX2, Q5YCC7, Q64448, Q69ZW3, Q6DR98, Q6H1V1, Q6IMP4, Q6TYA8, Q7TQ69, Q7Z5M5, Q86B91, Q8INR6

Diamond homologs: A2A2Y4, A2AD83, A2ALK8, B2RYE5, F1LYQ8, F1P065, F8VPU2, O43491, O57457, O70318, O94887, P11171, P11434, P26045, P28191, P29074, P48193, P52963, Q0P4Q4, Q54K81, Q58CU2, Q5FVG2, Q5R803, Q5RAB8, Q6P5H6, Q6Q7P4, Q6ZUT3, Q7Z6J6, Q8BGS1, Q8BHD4, Q91VS8, Q9H329, Q9H4G0, Q9HCM4, Q9HCS5, Q9JMC8, Q9MYU8, Q9N179, Q9V8R9, Q9WTP0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
Intrinsic Pathway for Apoptosis	5	22.2×	2e-04
Apoptosis	7	17.8×	3e-05
Programmed Cell Death	8	17.8×	7e-06
Transcriptional and post-translational regulation of MITF-M expression and activity	5	13.5×	2e-03
Extra-nuclear estrogen signaling	5	12.9×	2e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	11.7×	2e-03
MITF-M-regulated melanocyte development	5	8.7×	8e-03
RHO GTPase Effectors	7	7.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	120
Likely benign	42
Benign	14

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
402208	NM_012156.2(EPB41L1):c.1912C>T (p.Arg638Cys)	Likely pathogenic

SpliceAI

3560 predictions. Top by Δscore:

Variant	Effect	Δscore
20:36154893:CCAG:C	donor_loss	1.0000
20:36154894:CAG:C	donor_loss	1.0000
20:36154895:AGGT:A	donor_loss	1.0000
20:36154896:GG:G	donor_loss	1.0000
20:36154898:T:G	donor_loss	1.0000
20:36173753:T:G	acceptor_gain	1.0000
20:36173762:A:AG	acceptor_gain	1.0000
20:36173762:AGGC:A	acceptor_gain	1.0000
20:36173763:G:GT	acceptor_gain	1.0000
20:36173763:GGC:G	acceptor_gain	1.0000
20:36173763:GGCG:G	acceptor_gain	1.0000
20:36173763:GGCGT:G	acceptor_gain	1.0000
20:36173951:ACAGG:A	donor_loss	1.0000
20:36173954:GGTG:G	donor_loss	1.0000
20:36173955:GTGT:G	donor_loss	1.0000
20:36175540:T:TA	acceptor_gain	1.0000
20:36175548:CA:C	acceptor_loss	1.0000
20:36175548:CAG:C	acceptor_gain	1.0000
20:36175549:A:AG	acceptor_gain	1.0000
20:36175549:A:T	acceptor_loss	1.0000
20:36175549:AGA:A	acceptor_gain	1.0000
20:36175550:G:A	acceptor_loss	1.0000
20:36175550:G:GG	acceptor_gain	1.0000
20:36175550:GA:G	acceptor_gain	1.0000
20:36175550:GAG:G	acceptor_gain	1.0000
20:36175550:GAGC:G	acceptor_gain	1.0000
20:36175694:G:GT	donor_gain	1.0000
20:36175695:GAGTA:G	donor_gain	1.0000
20:36175697:G:GG	donor_gain	1.0000
20:36175703:GT:G	donor_gain	1.0000

AlphaMissense

5809 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:36175675:T:A	V101D	1.000
20:36177965:G:A	G119D	1.000
20:36177986:T:A	V126D	1.000
20:36178004:T:C	L132P	1.000
20:36178028:T:C	L140P	1.000
20:36178633:T:A	W151R	1.000
20:36178633:T:C	W151R	1.000
20:36178637:T:C	L152P	1.000
20:36182299:T:A	V173D	1.000
20:36182304:T:C	F175L	1.000
20:36182306:C:A	F175L	1.000
20:36182306:C:G	F175L	1.000
20:36182329:T:C	L183P	1.000
20:36185125:T:C	L192P	1.000
20:36185131:T:C	L194P	1.000
20:36185137:T:C	L196P	1.000
20:36185140:G:C	R197P	1.000
20:36185191:T:C	L214P	1.000
20:36185194:T:C	L215P	1.000
20:36185196:G:C	G216R	1.000
20:36185197:G:A	G216D	1.000
20:36185299:T:C	L250P	1.000
20:36185320:T:C	L257P	1.000
20:36187695:G:C	A269P	1.000
20:36187708:T:C	F273S	1.000
20:36187729:T:C	L280P	1.000
20:36187759:C:A	A290D	1.000
20:36188347:G:C	D292H	1.000
20:36188347:G:T	D292Y	1.000
20:36188348:A:C	D292A	1.000

dbSNP variants (sampled 300 via entrez): RS1000012458 (20:36117583 A>T), RS1000020348 (20:36208965 G>A), RS1000136879 (20:36124528 T>A), RS1000147018 (20:36215664 C>T), RS1000181860 (20:36091570 C>T), RS1000191002 (20:36094285 T>G), RS1000209351 (20:36143339 C>T), RS1000227206 (20:36139894 G>A), RS1000264291 (20:36098438 C>T), RS1000275100 (20:36206109 G>A,C,T), RS1000298161 (20:36130246 T>G), RS1000298959 (20:36124306 A>G), RS1000302749 (20:36143069 G>A), RS1000304630 (20:36205801 G>C), RS1000305776 (20:36184315 T>C)

Disease associations

OMIM: gene MIM:602879 | disease phenotypes: MIM:614257

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant
intellectual disability, autosomal dominant 11	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	AD

Mondo (4): intellectual disability, autosomal dominant 11 (MONDO:0013658), complex neurodevelopmental disorder (MONDO:0100038), intellectual disability (MONDO:0001071), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (2): Non-specific syndromic intellectual disability (Orphanet:528084), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000490	Deeply set eye
HP:0000708	Atypical behavior
HP:0001156	Brachydactyly
HP:0001181	Adducted thumb
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001511	Intrauterine growth retardation
HP:0001775	Tarsal osteovalgus
HP:0002007	Frontal bossing
HP:0008872	Feeding difficulties in infancy
HP:0010864	Severe intellectual disability
HP:0011800	Midface retrusion
HP:0012385	Camptodactyly
HP:0040019	Finger clinodactyly

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001956_21	Height	6.000000e-12
GCST004066_25	Hip circumference	8.000000e-07
GCST004066_99	Hip circumference	1.000000e-09
GCST008870_2	Keratinocyte cancer (MTAG)	6.000000e-32
GCST010002_66	Refractive error	2.000000e-20
GCST012227_1150	Hip circumference adjusted for BMI	2.000000e-08
GCST012227_1152	Hip circumference adjusted for BMI	9.000000e-26
GCST012227_1153	Hip circumference adjusted for BMI	7.000000e-09
GCST012227_1154	Hip circumference adjusted for BMI	2.000000e-15
GCST90013410_68	Basal cell carcinoma	4.000000e-20
GCST90020028_1567	Hip circumference adjusted for BMI	4.000000e-08
GCST90020028_1568	Hip circumference adjusted for BMI	2.000000e-08
GCST90020029_196	Waist circumference adjusted for body mass index	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010176	keratinocyte carcinoma
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	7
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	3
Tretinoin	decreases expression, increases expression	3
bisphenol A	decreases methylation, increases expression	2
Arsenic Trioxide	decreases response to substance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
terbufos	increases methylation	1
trichostatin A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1