EMC10

Summary

EMC10 (ER membrane protein complex subunit 10, HGNC:27609) is a protein-coding gene on chromosome 19q13.33, encoding ER membrane protein complex subunit 10 (Q5UCC4). Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins.

Contributes to membrane insertase activity. Involved in positive regulation of angiogenesis; positive regulation of endothelial cell proliferation; and protein insertion into ER membrane. Located in endoplasmic reticulum membrane and extracellular region. Part of EMC complex.

Source: NCBI Gene 284361 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with dysmorphic facies and variable seizures (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 97 total — 8 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_206538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27609
Approved symbol	EMC10
Name	ER membrane protein complex subunit 10
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	INM02, HSS1, HSM1
Ensembl gene	ENSG00000161671
Ensembl biotype	protein_coding
OMIM	614545
Entrez	284361

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000334976, ENST00000376918, ENST00000594508, ENST00000597426, ENST00000597799, ENST00000598585, ENST00000599293, ENST00000601780

RefSeq mRNA: 2 — MANE Select: NM_206538 NM_175063, NM_206538

CCDS: CCDS12796, CCDS42594

Canonical transcript exons

ENST00000334976 — 7 exons

Exon	Start	End
ENSE00000000104	50476507	50476658
ENSE00003076853	50482149	50490871
ENSE00003578027	50477929	50478001
ENSE00003595604	50480111	50480215
ENSE00003609184	50480581	50480762
ENSE00003657381	50480884	50480977
ENSE00003690247	50478957	50479066

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.3631 / max 560.4942, expressed in 1807 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177153	68.3590	1807
177152	8.0041	1732

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	98.48	gold quality
pituitary gland	UBERON:0000007	98.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.67	gold quality
left lobe of thyroid gland	UBERON:0001120	97.45	gold quality
right lobe of thyroid gland	UBERON:0001119	97.37	gold quality
right coronary artery	UBERON:0001625	97.34	gold quality
descending thoracic aorta	UBERON:0002345	97.28	gold quality
thoracic aorta	UBERON:0001515	97.22	gold quality
ascending aorta	UBERON:0001496	97.18	gold quality
right testis	UBERON:0004534	96.94	gold quality
metanephros cortex	UBERON:0010533	96.93	gold quality
stromal cell of endometrium	CL:0002255	96.79	gold quality
right adrenal gland	UBERON:0001233	96.68	gold quality
aorta	UBERON:0000947	96.67	gold quality
left adrenal gland	UBERON:0001234	96.67	gold quality
left adrenal gland cortex	UBERON:0035825	96.65	gold quality
right adrenal gland cortex	UBERON:0035827	96.65	gold quality
left testis	UBERON:0004533	96.61	gold quality
thyroid gland	UBERON:0002046	96.58	gold quality
mucosa of transverse colon	UBERON:0004991	96.49	gold quality
popliteal artery	UBERON:0002250	96.37	gold quality
tibial artery	UBERON:0007610	96.37	gold quality
spinal cord	UBERON:0002240	96.35	gold quality
left ovary	UBERON:0002119	96.20	gold quality
right ovary	UBERON:0002118	96.19	gold quality
left coronary artery	UBERON:0001626	96.14	gold quality
body of stomach	UBERON:0001161	96.12	gold quality
right atrium auricular region	UBERON:0006631	96.08	gold quality
adrenal cortex	UBERON:0001235	95.82	gold quality
coronary artery	UBERON:0001621	95.75	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	27.94
E-CURD-114	yes	11.44
E-HCAD-8	no	348.42
E-HCAD-31	no	19.11
E-ENAD-27	no	3.75
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU2F1, POU2F2

miRNA regulators (miRDB)

44 targeting EMC10, 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-4455	100.00	65.48	1587
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-6884-3P	98.05	65.32	750

Literature-anchored findings (GeneRIF, showing 11)

• as a novel secreted protein, INM02 is associated with functions of pancreatic islets, especially of beta-cells (PMID:19570817)
• High-expression of hHSS1 is associated high-grade gliomas. (PMID:20680400)
• hHSS1-overexpression modulates signaling pathways involved in tumorigenesis. (PMID:25481245)
• Sperm EMC10 levels are positively associated with sperm motility in human. (PMID:29659949)
• EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay. (PMID:32869858)
• A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features. (PMID:33531666)
• An engineered transcriptional reporter of protein localization identifies regulators of mitochondrial and ER membrane protein trafficking in high-throughput CRISPRi screens. (PMID:34414886)
• The phenotype of homozygous EMC10 variant: A new syndrome with intellectual disability and language impairment. (PMID:35124540)
• Biallelic loss of EMC10 leads to mild to severe intellectual disability. (PMID:35684946)
• Membrane-Bound EMC10 Is Required for Sperm Motility via Maintaining the Homeostasis of Cytoplasm Sodium in Sperm. (PMID:36077468)
• Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice. (PMID:36443308)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	emc10	ENSDARG00000054793
mus_musculus	Emc10	ENSMUSG00000008140
rattus_norvegicus	Emc10	ENSRNOG00000019532

Protein

Protein identifiers

ER membrane protein complex subunit 10 — Q5UCC4 (reviewed: Q5UCC4)

Alternative names: Hematopoietic signal peptide-containing membrane domain-containing protein 1

All UniProt accessions (5): Q5UCC4, M0QYY4, M0R030, M0R1B7, M0R2A0

UniProt curated annotations — full annotation on UniProt →

Function. Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. Promotes angiogenesis and tissue repair in the heart after myocardial infarction. Stimulates cardiac endothelial cell migration and outgrowth via the activation of p38 MAPK, PAK and MAPK2 signaling pathways.

Subunit / interactions. Component of the ER membrane protein complex (EMC).

Subcellular location. Endoplasmic reticulum membrane Secreted.

Tissue specificity. Present in serum (at protein level). Increased expression seen in the left ventrice after myocardial infarction (at protein level). Expressed in the pituitary gland. Expressed in brain.

Post-translational modifications. Glycosylated.

Disease relevance. Neurodevelopmental disorder with dysmorphic facies and variable seizures (NEDDFAS) [MIM:619264] An autosomal recessive disorder characterized by global developmental delay apparent in early childhood, mildly impaired intellectual development, speech delay, behavioral abnormalities, and non-specific dysmorphic facial features. Some patients may have seizures, brain imaging abnormalities, mild skeletal defects, and renal abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the EMC10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5UCC4-1	1, HSM1	yes
Q5UCC4-2	2, Hematopoietic signal peptide-containing secreted protein 1, HSS1

RefSeq proteins (2): NP_778233, NP_996261* (*=MANE)

Domains & families (InterPro)

Pfam: PF21203

UniProt features (25 total): strand 10, turn 3, helix 3, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8J0O	ELECTRON MICROSCOPY	3.32
7ADO	ELECTRON MICROSCOPY	3.39
6WW7	ELECTRON MICROSCOPY	3.4
8EOI	ELECTRON MICROSCOPY	3.4
8J0N	ELECTRON MICROSCOPY	3.47
7ADP	ELECTRON MICROSCOPY	3.6
8S9S	ELECTRON MICROSCOPY	3.6
9ZZ6	ELECTRON MICROSCOPY	4.16
6Z3W	ELECTRON MICROSCOPY	6.4
9C7V	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5UCC4-F1	79.60	0.53

Functional residue map

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

Glycosylation sites (1): 182

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 181 (showing top): TGCGCANK_UNKNOWN, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION, STARK_HYPPOCAMPUS_22Q11_DELETION_UP, GTGCCTT_MIR506, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS

GO Biological Process (6): angiogenesis (GO:0001525), positive regulation of endothelial cell proliferation (GO:0001938), positive regulation of endothelial cell migration (GO:0010595), protein insertion into ER membrane by stop-transfer membrane-anchor sequence (GO:0045050), positive regulation of angiogenesis (GO:0045766), tail-anchored membrane protein insertion into ER membrane (GO:0071816)

GO Molecular Function (1): membrane insertase activity (GO:0032977)

GO Cellular Component (5): extracellular region (GO:0005576), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), EMC complex (GO:0072546), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein insertion into ER membrane	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
establishment of protein localization to membrane	1
protein carrier activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum membrane	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMC10	MMGT1	Q8N4V1	800
EMC10	EMC7	Q9NPA0	786
EMC10	EMC4	Q5J8M3	731
EMC10	EMC1	Q8N766	723
EMC10	EMC6	Q9BV81	716
EMC10	EMC2	Q15006	710
EMC10	EMC3	Q9P0I2	710
EMC10	EMC8	O43402	708
EMC10	EMC9	Q9Y3B6	689
EMC10	BTNL2	Q9UIR0	598
EMC10	CENPB	P07199	582
EMC10	GARIN5A	Q6IPT2	566
EMC10	CBX1	P23197	494
EMC10	CENPA	P49450	494
EMC10	FAM8A1	Q9UBU6	490
EMC10	CENPC	Q03188	490

IntAct

51 interactions, top by confidence:

A	B	Type	Score
EMC2	EMC8	psi-mi:“MI:0914”(association)	0.940
EMC8	EMC2	psi-mi:“MI:0914”(association)	0.940
EMC2	EMC10	psi-mi:“MI:0914”(association)	0.800
EMC7	EMC8	psi-mi:“MI:0914”(association)	0.790
MMGT1	EMC8	psi-mi:“MI:0914”(association)	0.730
EMC3	EMC8	psi-mi:“MI:0914”(association)	0.730
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
EMC4	EMC8	psi-mi:“MI:0914”(association)	0.640
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
EMC1	EMC8	psi-mi:“MI:0914”(association)	0.640
EMC9	EMC4	psi-mi:“MI:0914”(association)	0.640
EMC10	EMC8	psi-mi:“MI:0915”(physical association)	0.620
EMC6	EMC8	psi-mi:“MI:0914”(association)	0.530
ADIPOQ	C1QL1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530

BioGRID (88): EMC10 (Affinity Capture-RNA), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC10 (Proximity Label-MS), EMC10 (Proximity Label-MS), EMC10 (Affinity Capture-MS), EMC10 (Affinity Capture-MS)

ESM2 similar proteins: A1A4M2, A4IFG4, A5D8P8, A6NKD9, A7E2M3, B4F7F3, E9Q6B2, F1MX48, F1SAM7, O97676, P18065, P36956, P47877, P49705, P56720, P56873, Q00709, Q00973, Q09200, Q0IHY5, Q15465, Q24JP5, Q2YD98, Q3TAS6, Q58CS8, Q5QQ49, Q5UCC4, Q60416, Q60698, Q641Q3, Q68FE7, Q6AYH6, Q6DVA0, Q6P7K5, Q6UKI2, Q6WVG3, Q80WF4, Q8IW70, Q8JGM4, Q8K064

Diamond homologs: A1A4M2, A5D8P8, A7E2M3, Q3TAS6, Q5UCC4, Q6AYH6, Q6P7K5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EMC10	“form complex”	“Endoplasmic reticulum membrane complex- EMC9 variant”	binding
EMC10	“form complex”	“Endoplasmic reticulum membrane complex, EMC8 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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.

GO biological processes:

GO term	Partners	Fold	FDR
tail-anchored membrane protein insertion into ER membrane	9	234.1×	2e-18

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	4
Uncertain significance	50
Likely benign	19
Benign	2

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1064428	NM_206538.4(EMC10):c.679-1G>A	Pathogenic
1320119	NM_206538.4(EMC10):c.343C>T (p.Arg115Ter)	Pathogenic
1324329	NM_206538.4(EMC10):c.289C>T (p.Arg97Ter)	Pathogenic
1704219	NM_206538.4(EMC10):c.543dup (p.Asn182fs)	Pathogenic
1704221	NM_206538.4(EMC10):c.259C>T (p.Gln87Ter)	Pathogenic
1704223	NM_206538.4(EMC10):c.188-2A>C	Pathogenic
2650346	NM_206538.4(EMC10):c.585-1G>T	Pathogenic
988592	NM_206538.4(EMC10):c.287del (p.Gly96fs)	Pathogenic
1320121	NM_206538.4(EMC10):c.70C>T (p.Arg24Ter)	Likely pathogenic
2585449	NM_206538.4(EMC10):c.554del (p.Val185fs)	Likely pathogenic
4292635	NM_206538.4(EMC10):c.130C>T (p.Arg44Ter)	Likely pathogenic
4526441	NM_206538.4(EMC10):c.124G>T (p.Glu42Ter)	Likely pathogenic

SpliceAI

1285 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50476656:GGG:G	donor_gain	1.0000
19:50476657:GGG:G	donor_gain	1.0000
19:50477927:AGGCT:A	acceptor_gain	1.0000
19:50477928:GGCT:G	acceptor_gain	1.0000
19:50477928:GGCTG:G	acceptor_gain	1.0000
19:50477997:GATCG:G	donor_gain	1.0000
19:50480103:A:AG	acceptor_gain	1.0000
19:50480104:T:G	acceptor_gain	1.0000
19:50480109:A:AG	acceptor_gain	1.0000
19:50480109:AG:A	acceptor_gain	1.0000
19:50480109:AGGAT:A	acceptor_gain	1.0000
19:50480110:G:A	acceptor_gain	1.0000
19:50480110:G:GT	acceptor_gain	1.0000
19:50480110:GGA:G	acceptor_gain	1.0000
19:50480110:GGAT:G	acceptor_gain	1.0000
19:50480110:GGATG:G	acceptor_gain	1.0000
19:50480211:CTGCG:C	donor_gain	1.0000
19:50480212:TGCG:T	donor_gain	1.0000
19:50480213:GCG:G	donor_gain	1.0000
19:50480213:GCGG:G	donor_gain	1.0000
19:50480214:CGGT:C	donor_loss	1.0000
19:50480216:G:GG	donor_gain	1.0000
19:50480216:GTG:G	donor_loss	1.0000
19:50480217:T:A	donor_loss	1.0000
19:50480577:ACAGT:A	acceptor_gain	1.0000
19:50480578:C:G	acceptor_gain	1.0000
19:50480578:CA:C	acceptor_loss	1.0000
19:50480579:A:AC	acceptor_loss	1.0000
19:50480579:A:AG	acceptor_gain	1.0000
19:50480579:AGT:A	acceptor_gain	1.0000

AlphaMissense

1642 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50482168:T:A	V233D	1.000
19:50482171:T:A	V234D	1.000
19:50480964:T:G	F222C	0.999
19:50480967:T:G	F223C	0.999
19:50482155:T:G	Y229D	0.999
19:50482159:T:A	I230N	0.999
19:50482162:T:A	I231N	0.999
19:50482165:C:A	P232H	0.999
19:50482165:C:G	P232R	0.999
19:50480142:T:A	V110D	0.998
19:50480973:A:T	K225I	0.998
19:50480974:A:C	K225N	0.998
19:50480974:A:T	K225N	0.998
19:50480975:T:C	Y226H	0.998
19:50480976:A:G	Y226C	0.998
19:50482149:T:A	W227R	0.998
19:50482149:T:C	W227R	0.998
19:50482155:T:C	Y229H	0.998
19:50480135:T:G	Y108D	0.997
19:50480145:G:C	R111P	0.997
19:50480615:T:C	L146P	0.997
19:50480900:T:C	F201L	0.997
19:50480901:T:G	F201C	0.997
19:50480902:C:A	F201L	0.997
19:50480902:C:G	F201L	0.997
19:50480967:T:C	F223S	0.997
19:50480972:A:G	K225E	0.997
19:50482151:G:C	W227C	0.997
19:50482151:G:T	W227C	0.997
19:50482177:T:C	F236S	0.997

dbSNP variants (sampled 300 via entrez): RS1000206290 (19:50491333 T>A,G), RS1000255206 (19:50479648 G>T), RS1000543072 (19:50483179 C>T), RS1000555390 (19:50482245 G>A,T), RS1000622769 (19:50482441 G>A), RS1000894287 (19:50486274 C>G,T), RS1000898221 (19:50486867 A>G), RS1000936339 (19:50486541 T>C), RS1001146212 (19:50482314 T>C), RS1001182839 (19:50478010 G>A), RS1001295528 (19:50490630 C>T), RS1001453201 (19:50482109 C>T), RS1001503147 (19:50485791 C>G,T), RS1001556627 (19:50482778 T>A,C,G), RS1001629720 (19:50481577 G>T)

Disease associations

OMIM: gene MIM:614545 | disease phenotypes: MIM:619264

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with dysmorphic facies and variable seizures	Definitive	Autosomal recessive
neurodevelopmental disorder	Strong	Autosomal recessive
global developmental delay with or without impaired intellectual development	Limited	Autosomal recessive

Mondo (4): neurodevelopmental disorder with dysmorphic facies and variable seizures (MONDO:0031011), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), global developmental delay with or without impaired intellectual development (MONDO:0032680)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000678	Dental crowding
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001007	Hirsutism
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001357	Plagiocephaly
HP:0002007	Frontal bossing
HP:0002360	Sleep disturbance
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0011463	Childhood onset
HP:0025116	Fetal distress
HP:0031987	Diminished ability to concentrate
HP:0100033	Tics

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009441_8	Age-related cognitive decline (memory) (slope of z-scores)	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression, increases methylation	4
bisphenol A	increases expression, decreases expression	2
deoxynivalenol	decreases expression	1
sodium arsenate	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Sodium Selenite	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1R2	Abcam HeLa EMC10 KO	Cancer cell line	Female
CVCL_F1JP	A-172 EMC10 isoform HSS1	Cancer cell line	Male
CVCL_F1JR	U-87MG EMC10 isoform HSS1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
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
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
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
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
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)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays