LMAN2L

Summary

LMAN2L (lectin, mannose binding 2 like, HGNC:19263) is a protein-coding gene on chromosome 2q11.2, encoding VIP36-like protein (Q9H0V9). May be involved in the regulation of export from the endoplasmic reticulum of a subset of glycoproteins.

This gene encodes a protein belonging to the L-type lectin group of type 1 membrane proteins, which function in the mammalian early secretory pathway. These proteins contain luminal carbohydrate recognition domains, which display homology to leguminous lectins. Unlike other proteins of the group, which cycle in the early secretory pathway and are predominantly associated with post endoplasmic reticulum membranes, the protein encoded by this gene is a non-cycling resident protein of the ER, where it functions as a cargo receptor for glycoproteins. It is proposed to regulate exchange of folded proteins for transport to the Golgi and exchange of misfolded glycoproteins for transport to the ubiquitin-proteasome pathway.

Source: NCBI Gene 81562 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal recessive 52 (Moderate, GenCC) — +3 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 86 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 13
• MANE Select transcript: NM_030805

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19263
Approved symbol	LMAN2L
Name	lectin, mannose binding 2 like
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp564L2423, VIPL
Ensembl gene	ENSG00000114988
Ensembl biotype	protein_coding
OMIM	609552
Entrez	81562

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron

ENST00000264963, ENST00000377079, ENST00000434524, ENST00000434865, ENST00000440610, ENST00000446780, ENST00000449221, ENST00000474494, ENST00000480869, ENST00000893540, ENST00000893541, ENST00000893542, ENST00000920371, ENST00000970312, ENST00000970313, ENST00000970314, ENST00000970315

RefSeq mRNA: 10 — MANE Select: NM_030805 NM_001142292, NM_001322346, NM_001322347, NM_001322350, NM_001322351, NM_001322352, NM_001322354, NM_001322355, NM_001322356, NM_030805

CCDS: CCDS2023, CCDS46365

Canonical transcript exons

ENST00000264963 — 8 exons

Exon	Start	End
ENSE00001948809	96705929	96707398
ENSE00003474580	96711656	96711770
ENSE00003499046	96734409	96734526
ENSE00003522678	96733519	96733601
ENSE00003557771	96737949	96738067
ENSE00003577284	96711864	96712025
ENSE00003585918	96707714	96707833
ENSE00003592181	96739854	96740064

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 89.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1701 / max 107.3570, expressed in 1762 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29764	8.1701	1762

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	89.36	gold quality
renal medulla	UBERON:0000362	89.09	gold quality
ovary	UBERON:0000992	88.24	gold quality
right ovary	UBERON:0002118	87.96	gold quality
pancreatic ductal cell	CL:0002079	87.87	silver quality
right uterine tube	UBERON:0001302	87.44	gold quality
right lobe of thyroid gland	UBERON:0001119	87.36	gold quality
left ovary	UBERON:0002119	87.34	gold quality
adenohypophysis	UBERON:0002196	87.09	gold quality
thyroid gland	UBERON:0002046	86.81	gold quality
fallopian tube	UBERON:0003889	86.79	gold quality
pituitary gland	UBERON:0000007	86.76	gold quality
heart left ventricle	UBERON:0002084	86.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.58	gold quality
nephron tubule	UBERON:0001231	86.58	gold quality
mucosa of transverse colon	UBERON:0004991	86.58	gold quality
cardiac ventricle	UBERON:0002082	86.40	gold quality
left lobe of thyroid gland	UBERON:0001120	86.39	gold quality
pericardium	UBERON:0002407	86.33	gold quality
apex of heart	UBERON:0002098	86.32	gold quality
cranial nerve II	UBERON:0000941	86.29	gold quality
endothelial cell	CL:0000115	86.20	gold quality
oviduct epithelium	UBERON:0004804	86.17	gold quality
choroid plexus epithelium	UBERON:0003911	86.15	gold quality
prostate gland	UBERON:0002367	86.13	gold quality
endocervix	UBERON:0000458	86.10	gold quality
adult mammalian kidney	UBERON:0000082	86.08	gold quality
metanephros	UBERON:0000081	85.95	gold quality
lower esophagus mucosa	UBERON:0035834	85.86	gold quality
right lobe of liver	UBERON:0001114	85.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2, RBPJ

miRNA regulators (miRDB)

49 targeting LMAN2L, 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-4673	100.00	66.64	1490
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-6808-5P	99.31	66.23	2150

Literature-anchored findings (GeneRIF, showing 6)

• VIPL terminates in the sequence KRFY, characteristic for proteins recycling between the ER and ERGIC/cis-Golgi; and knock-down of VIPL mRNA slowed secretion of two glycoproteins (35 and 250 kDa), suggesting that VIPL may function as an ER export receptor. (PMID:12878160)
• selective interaction of VIPL and VIP36 with the deglucosylated trimannose in the D1 branch of high-mannose-type oligosaccharides but with different pH dependence. (PMID:18025080)
• The results of this study suggested that significant novel association signals near the genes LMAN2L and provide supportive evidence for the previously reported association signals near ANK3 and within the 3p21.1 locus. (PMID:22182935)
• Study showed a significant association between LMAN2L and risk of both bipolar disorder and schizophrenia (PMID:24914473)
• Homozygous missense mutation p.R53Q in the LMAN2L gene causes autosomal recessive intellectual disability and seizures. (PMID:26566883)
• segregate a NM_001142292.1:c.1073delT mutation that eliminates LMAN2L’s endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane (PMID:31020005)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lman2lb	ENSDARG00000088663
danio_rerio	lman2la	ENSDARG00000102657
mus_musculus	Lman2l	ENSMUSG00000001143
rattus_norvegicus	Lman2l	ENSRNOG00000015699
drosophila_melanogaster	CG5510	FBGN0039160
caenorhabditis_elegans		WBGENE00002071

Paralogs (3): LMAN1 (ENSG00000074695), LMAN1L (ENSG00000140506), LMAN2 (ENSG00000169223)

Protein

Protein identifiers

VIP36-like protein — Q9H0V9 (reviewed: Q9H0V9)

Alternative names: Lectin mannose-binding 2-like

All UniProt accessions (5): Q9H0V9, F2Z2L5, F8WB07, F8WCX4, F8WEK5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the regulation of export from the endoplasmic reticulum of a subset of glycoproteins. May function as a regulator of ERGIC-53.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane.

Tissue specificity. Expressed in numerous tissues. Highest expression in skeletal muscle and kidney, intermediate levels in heart, liver and placenta, low levels in brain, thymus, spleen, small intestine and lung.

Disease relevance. Intellectual developmental disorder, autosomal recessive 52 (MRT52) [MIM:616887] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT52 clinical features include global developmental delay, severe intellectual disability with poor speech, and mild seizures in early childhood. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, autosomal dominant 69 (MRD69) [MIM:617863] An autosomal dominant disorder characterized by developmental delay and variably impaired intellectual development. Additional features may include intention tremor in infancy and seizures in childhood, with remission of these in adolescence. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H0V9-1	1	yes
Q9H0V9-2	2
Q9H0V9-3	3

RefSeq proteins (10): NP_001135764, NP_001309275, NP_001309276, NP_001309279, NP_001309280, NP_001309281, NP_001309283, NP_001309284, NP_001309285, NP_110432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005052	Lectin_leg	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR051136	Intracellular_Lectin-GPT	Family

Pfam: PF03388

UniProt features (27 total): binding site 9, sequence conflict 4, splice variant 3, topological domain 2, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1, sequence variant 1, mutagenesis site 1, transmembrane region 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0V9-F1	84.90	0.66

Functional residue map

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

Ligand- & substrate-binding residues (9): 161–163; 161; 163; 188; 191; 258–260; 93; 128; 159

Disulfide bonds (1): 200–237

Glycosylation sites (1): 181

Mutagenesis-validated functional residues (1):

Position	Phenotype
344–346	loss of er retention.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-5694530	Cargo concentration in the ER
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 154 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PROTEIN_MATURATION, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOCC_COATED_VESICLE, ZIC1_01, GOBP_PROTEIN_FOLDING, TIEN_INTESTINE_PROBIOTICS_24HR_UP, TGCCTTA_MIR124A, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ENDOPLASMIC_RETICULUM_GOLGI_INTERMEDIATE_COMPARTMENT, GOCC_ORGANELLE_SUBCOMPARTMENT, GOBP_GOLGI_VESICLE_TRANSPORT

GO Biological Process (3): protein folding (GO:0006457), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), protein transport (GO:0015031)

GO Molecular Function (4): D-mannose binding (GO:0005537), metal ion binding (GO:0046872), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (7): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), membrane (GO:0016020), COPII-coated ER to Golgi transport vesicle (GO:0030134), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
intracellular membrane-bounded organelle	3
binding	2
endomembrane system	2
cellular process	1
protein maturation	1
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
monosaccharide binding	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
coated vesicle	1

Protein interactions and networks

STRING

1232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMAN2L	MCFD2	Q8NI22	772
LMAN2L	TRANK1	O15050	549
LMAN2L	LMAN1	P49257	528
LMAN2L	ERLEC1	Q96DZ1	482
LMAN2L	FAHD2B	Q6P2I3	478
LMAN2L	MOGS	Q13724	475
LMAN2L	ANKRD39	Q53RE8	447
LMAN2L	FAM178B	Q8IXR5	447
LMAN2L	FER1L5	A0AVI2	445
LMAN2L	CANX	P27824	430
LMAN2L	ANKMY2	Q8IV38	413
LMAN2L	OS9	Q13438	410
LMAN2L	PPP2R5C	Q13362	406
LMAN2L	SLC8B1	Q6J4K2	406
LMAN2L	RNF135	Q8IUD6	405

IntAct

109 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
MAL	LMAN2L	psi-mi:“MI:0915”(physical association)	0.560
HTT	LMAN2L	psi-mi:“MI:0915”(physical association)	0.560
LMAN2L		psi-mi:“MI:0915”(physical association)	0.550
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
LINGO2	GAPDHS	psi-mi:“MI:0914”(association)	0.530
TOR1B	CLGN	psi-mi:“MI:0914”(association)	0.530
PLVAP	SMPD2	psi-mi:“MI:0914”(association)	0.530
ASGR2	MT-CO1	psi-mi:“MI:0914”(association)	0.530
ANO6	CDC27	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
LINGO1	LGALS8	psi-mi:“MI:0914”(association)	0.530
CD63	LGALS8	psi-mi:“MI:0914”(association)	0.530
IL27RA	AP1G2	psi-mi:“MI:0914”(association)	0.530
LINGO2	LGALS1	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
TMEM106A	B4GALT3	psi-mi:“MI:0914”(association)	0.530
TOR1A	TOR1B	psi-mi:“MI:0914”(association)	0.530
LMAN2L	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.370
Csk	FRYL	psi-mi:“MI:0914”(association)	0.350
Homer1	KIF3B	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (145): LMAN2L (Two-hybrid), LMAN2L (Affinity Capture-MS), LMAN2L (Affinity Capture-MS), LMAN2L (Co-fractionation), LMAN2L (Affinity Capture-MS), LMAN2L (Affinity Capture-MS), PTGS2 (Affinity Capture-MS), CNTNAP1 (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), SUSD1 (Affinity Capture-MS), TMEM245 (Affinity Capture-MS), LMAN2L (Affinity Capture-MS), LMAN2L (Affinity Capture-MS), TENM3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4K5, A8MWY0, F1QR43, O13097, O15041, O18756, O73874, P11456, P20645, P24668, P49256, P49257, P52795, P52796, P79282, Q12907, Q13822, Q14165, Q2HJD1, Q3UZV7, Q5FVQ4, Q5NVB3, Q5RCF0, Q62902, Q64610, Q659X0, Q6AY20, Q6BEA0, Q6EV76, Q6EV77, Q6GMK0, Q6INX3, Q6PCX7, Q6ZQI3, Q80UG2, Q812F8, Q8BJQ9, Q8R4K8, Q8TDX6, Q9BYC5

Diamond homologs: O94401, P49256, P59481, Q12907, Q2HJD1, Q5RCF0, Q9H0V9, P49257, Q5FB95, Q62902, Q8VCD3, Q9D0F3, Q9DBH5, Q9HAT1, Q9TU32

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	5	24.0×	6e-04
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	7.4×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	6	17.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	62
Likely benign	14
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1695987	NM_030805.4(LMAN2L):c.1040del (p.Phe347fs)	Pathogenic
224890	NM_030805.4(LMAN2L):c.158G>A (p.Arg53Gln)	Pathogenic
831980	NC_000002.12:g.(?96733519)(96832047_?)del	Pathogenic
1710494	NM_030805.4(LMAN2L):c.740G>A (p.Arg247His)	Likely pathogenic

SpliceAI

1664 predictions. Top by Δscore:

Variant	Effect	Δscore
2:96707399:C:CC	acceptor_gain	1.0000
2:96707712:A:AC	donor_gain	1.0000
2:96707713:C:CC	donor_gain	1.0000
2:96707713:CT:C	donor_gain	1.0000
2:96707713:CTCT:C	donor_gain	1.0000
2:96711650:CAGTA:C	donor_loss	1.0000
2:96711651:AGTAC:A	donor_loss	1.0000
2:96711652:GTA:G	donor_loss	1.0000
2:96711653:TA:T	donor_loss	1.0000
2:96711654:AC:A	donor_loss	1.0000
2:96711655:C:CT	donor_loss	1.0000
2:96711766:ATTAT:A	acceptor_gain	1.0000
2:96711767:TTAT:T	acceptor_gain	1.0000
2:96711768:TAT:T	acceptor_gain	1.0000
2:96711769:AT:A	acceptor_gain	1.0000
2:96711769:ATCTA:A	acceptor_loss	1.0000
2:96711770:TC:T	acceptor_loss	1.0000
2:96711771:C:CC	acceptor_gain	1.0000
2:96711776:A:AC	acceptor_gain	1.0000
2:96711858:TCTCA:T	donor_loss	1.0000
2:96711859:CTCAC:C	donor_loss	1.0000
2:96711861:CACC:C	donor_loss	1.0000
2:96712021:ACCCG:A	acceptor_gain	1.0000
2:96712022:CCCG:C	acceptor_gain	1.0000
2:96712022:CCCGC:C	acceptor_gain	1.0000
2:96712023:CCG:C	acceptor_gain	1.0000
2:96712023:CCGC:C	acceptor_gain	1.0000
2:96712024:CG:C	acceptor_gain	1.0000
2:96712024:CGC:C	acceptor_gain	1.0000
2:96712026:C:CC	acceptor_gain	1.0000

AlphaMissense

2273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:96734436:A:G	W133R	1.000
2:96734436:A:T	W133R	1.000
2:96734454:C:A	G127W	1.000
2:96711661:A:G	L260P	0.999
2:96711676:G:T	S255Y	0.999
2:96711679:G:A	S254F	0.999
2:96711679:G:T	S254Y	0.999
2:96711685:C:T	G252D	0.999
2:96711712:A:T	V243D	0.999
2:96711729:G:C	C237W	0.999
2:96711730:C:T	C237Y	0.999
2:96711731:A:G	C237R	0.999
2:96711868:A:G	L222S	0.999
2:96711934:C:G	C200S	0.999
2:96711935:A:G	C200R	0.999
2:96711935:A:T	C200S	0.999
2:96712017:G:C	F172L	0.999
2:96712017:G:T	F172L	0.999
2:96712019:A:G	F172L	0.999
2:96733565:A:G	L154P	0.999
2:96733568:C:T	G153E	0.999
2:96733569:C:A	G153W	0.999
2:96733569:C:G	G153R	0.999
2:96733569:C:T	G153R	0.999
2:96733573:A:C	F151L	0.999
2:96733573:A:T	F151L	0.999
2:96733575:A:G	F151L	0.999
2:96733589:C:A	G146V	0.999
2:96733589:C:T	G146E	0.999
2:96734441:G:T	A131E	0.999

dbSNP variants (sampled 300 via entrez): RS1000084782 (2:96741309 T>C), RS1000201061 (2:96721290 T>C), RS1000299277 (2:96736715 T>C), RS1000331204 (2:96730078 T>A), RS1000403239 (2:96730517 T>C), RS1000449798 (2:96741397 G>A), RS1000516178 (2:96736730 C>A,G), RS1000577147 (2:96724564 G>A), RS1000731628 (2:96731663 T>A), RS1000847794 (2:96706028 T>G), RS1000939622 (2:96712587 G>T), RS1000955240 (2:96712977 C>A,T), RS1001095143 (2:96720440 G>A,C), RS1001116182 (2:96730658 A>C), RS1001188283 (2:96730812 C>T)

Disease associations

OMIM: gene MIM:609552 | disease phenotypes: MIM:616887, MIM:617863, MIM:615716

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 52	Moderate	Autosomal recessive
intellectual developmental disorder, autosomal dominant 69	Moderate	Autosomal dominant
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (6): intellectual disability, autosomal recessive 52 (MONDO:0014815), intellectual developmental disorder, autosomal dominant 69 (MONDO:0029465), neurodevelopmental disorder (MONDO:0700092), hyperphosphatasia with intellectual disability syndrome 4 (MONDO:0014318), complex neurodevelopmental disorder (MONDO:0100038), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (2): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Hyperphosphatasia-intellectual disability syndrome (Orphanet:247262)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000718	Aggressive behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0002069	Bilateral tonic-clonic seizure
HP:0002080	Intention tremor
HP:0003593	Infantile onset
HP:0007018	Attention deficit hyperactivity disorder
HP:0010864	Severe intellectual disability

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001241_9	Bipolar disorder	2.000000e-06
GCST001358_2	Bipolar disorder	2.000000e-10
GCST003962_1	Bipolar disorder	3.000000e-10
GCST006585_108	Blood protein levels	2.000000e-12
GCST006865_6	Bipolar disorder	3.000000e-06
GCST008103_13	Bipolar disorder	4.000000e-09
GCST009600_30	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-09
GCST012465_37	Bipolar disorder	5.000000e-11

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Ozone	increases abundance, affects expression, affects cotreatment, increases oxidation	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

204 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,
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
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
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
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
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
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism