GRAMD1B

Summary

GRAMD1B (GRAM domain containing 1B, HGNC:29214) is a protein-coding gene on chromosome 11q24.1, encoding Protein Aster-B (Q3KR37). Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER).

Predicted to enable cholesterol binding activity; cholesterol transfer activity; and phospholipid binding activity. Predicted to be involved in cellular response to cholesterol; cholesterol homeostasis; and intracellular sterol transport. Located in endoplasmic reticulum membrane; endoplasmic reticulum-plasma membrane contact site; and plasma membrane.

Source: NCBI Gene 57476 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 114 total — 1 likely-pathogenic
• MANE Select transcript: NM_001387025

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29214
Approved symbol	GRAMD1B
Name	GRAM domain containing 1B
Location	11q24.1
Locus type	gene with protein product
Status	Approved
Aliases	LAMb, KIAA1201
Ensembl gene	ENSG00000023171
Ensembl biotype	protein_coding
OMIM	620179
Entrez	57476

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000450171, ENST00000456860, ENST00000525757, ENST00000525945, ENST00000529432, ENST00000529750, ENST00000532581, ENST00000533341, ENST00000534764, ENST00000632815, ENST00000633087, ENST00000633646, ENST00000635736, ENST00000638086, ENST00000638157, ENST00000640939, ENST00000646146, ENST00000943461, ENST00000943462, ENST00000943463, ENST00000943464, ENST00000943465

RefSeq mRNA: 20 — MANE Select: NM_001387025 NM_001286563, NM_001286564, NM_001330396, NM_001354837, NM_001367418, NM_001367419, NM_001367420, NM_001367421, NM_001387024, NM_001387025, NM_001387026, NM_001387028, NM_001387029, NM_001387030, NM_001387031, NM_001387032, NM_001387033, NM_001387034, NM_001387035, NM_020716

CCDS: CCDS53720, CCDS66253, CCDS66254, CCDS81640, CCDS86254, CCDS91613

Canonical transcript exons

ENST00000635736 — 20 exons

Exon	Start	End
ENSE00002166971	123430269	123431166
ENSE00003496049	123613455	123613658
ENSE00003497524	123618693	123618800
ENSE00003498135	123594082	123594166
ENSE00003505027	123610196	123610338
ENSE00003512472	123577367	123577577
ENSE00003534215	123614745	123614835
ENSE00003543675	123584312	123584332
ENSE00003548147	123603426	123603541
ENSE00003552104	123612761	123612864
ENSE00003556962	123600468	123600548
ENSE00003561313	123619107	123619224
ENSE00003583234	123609795	123609913
ENSE00003590001	123606609	123606798
ENSE00003625135	123595942	123596037
ENSE00003625161	123608659	123608802
ENSE00003661834	123605322	123605478
ENSE00003789011	123594735	123594838
ENSE00003794647	123480816	123480893
ENSE00003801168	123622506	123627767

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8733 / max 392.8682, expressed in 1307 samples.

FANTOM5 promoters (40 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117281	2.2532	722
117309	1.2449	151
117279	0.9188	322
117282	0.8814	447
117298	0.8318	225
117292	0.7344	145
117283	0.6214	257
117300	0.5893	139
117286	0.4612	221
117280	0.4429	175

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.24	gold quality
left adrenal gland	UBERON:0001234	97.77	gold quality
right adrenal gland	UBERON:0001233	97.75	gold quality
paraflocculus	UBERON:0005351	97.71	gold quality
right adrenal gland cortex	UBERON:0035827	97.61	gold quality
adrenal cortex	UBERON:0001235	97.60	gold quality
left adrenal gland cortex	UBERON:0035825	97.53	gold quality
trigeminal ganglion	UBERON:0001675	97.19	gold quality
cerebellum	UBERON:0002037	97.17	gold quality
cerebellar hemisphere	UBERON:0002245	97.09	gold quality
cerebellar cortex	UBERON:0002129	97.07	gold quality
adrenal gland	UBERON:0002369	96.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.99	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.90	gold quality
dorsal root ganglion	UBERON:0000044	96.71	gold quality
parietal lobe	UBERON:0001872	95.03	gold quality
postcentral gyrus	UBERON:0002581	94.95	gold quality
CA1 field of hippocampus	UBERON:0003881	94.72	gold quality
pons	UBERON:0000988	94.58	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.20	gold quality
olfactory bulb	UBERON:0002264	94.10	gold quality
superior frontal gyrus	UBERON:0002661	94.08	gold quality
occipital lobe	UBERON:0002021	93.60	gold quality
frontal pole	UBERON:0002795	93.40	gold quality
orbitofrontal cortex	UBERON:0004167	93.39	gold quality
primary visual cortex	UBERON:0002436	93.35	gold quality
lateral globus pallidus	UBERON:0002476	93.22	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.19	gold quality
middle temporal gyrus	UBERON:0002771	93.01	gold quality
entorhinal cortex	UBERON:0002728	92.98	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	50.65
E-MTAB-5061	yes	13.42
E-GEOD-81608	yes	8.81
E-GEOD-83139	yes	4.23
E-ANND-3	no	6.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

297 targeting GRAMD1B, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3667-3P	99.99	67.17	1636

Literature-anchored findings (GeneRIF, showing 5)

• GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling (PMID:29934528)
• Circular RNA circGRAMD1B inhibits gastric cancer progression by sponging miR-130a-3p and regulating PTEN and p21 expression. (PMID:31719211)
• Aster-B coordinates with Arf1 to regulate mitochondrial cholesterol transport. (PMID:32738348)
• Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b. (PMID:33604931)
• Aster proteins mediate carotenoid transport in mammalian cells. (PMID:35394870)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gramd1bb	ENSDARG00000074258
danio_rerio	gramd1ba	ENSDARG00000075383
mus_musculus	Gramd1b	ENSMUSG00000040111
rattus_norvegicus	Gramd1b	ENSRNOG00000053577
drosophila_melanogaster	GramD1B	FBGN0085423
caenorhabditis_elegans	ZC328.3	WBGENE00022593

Paralogs (4): GRAMD1A (ENSG00000089351), GRAMD2B (ENSG00000155324), GRAMD2A (ENSG00000175318), GRAMD1C (ENSG00000178075)

Protein

Protein identifiers

Protein Aster-B — Q3KR37 (reviewed: Q3KR37)

Alternative names: GRAM domain-containing protein 1B

All UniProt accessions (11): A0A024R3M2, A0A0J9YXF6, A0A0J9YXZ1, A0A0J9YY71, A0A1B0GUD6, A0A1B0GVV0, A0A1B0GWG7, Q3KR37, A0A1W2PQ30, A0A2R8Y5X2, E9PRD6

UniProt curated annotations — full annotation on UniProt →

Function. Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER. Plays a crucial role in cholesterol homeostasis in the adrenal gland and has the unique ability to localize to the PM based on the level of membrane cholesterol. In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain. At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane.

Domain organisation. GRAM domain binds phosphatidylserine in the PM and mediates protein recruitment to endoplasmic reticulum-plasma membrane contact sites (EPCS) in response to excess cholesterol in the PM. VASt (VAD1 Analog of StAR-related lipid transfer) domain, also known as ASTER (Greek for star) domain is a sterol-binding domain.

Isoforms (4)

UniProt ID	Names	Canonical?
Q3KR37-1	1	yes
Q3KR37-2	2
Q3KR37-3	3
Q3KR37-4	4

RefSeq proteins (20): NP_001273492, NP_001273493, NP_001317325, NP_001341766, NP_001354347, NP_001354348, NP_001354349, NP_001354350, NP_001373953, NP_001373954, NP_001373955, NP_001373957, NP_001373958, NP_001373959, NP_001373960, NP_001373961, NP_001373962, NP_001373963, NP_001373964, NP_065767 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004182	GRAM	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR031968	VASt	Domain
IPR051482	Cholesterol_transport	Family

Pfam: PF02893, PF16016

UniProt features (28 total): modified residue 9, compositionally biased region 6, splice variant 5, region of interest 3, domain 2, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3KR37-F1	68.76	0.34

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 (9): 28, 30, 274, 389, 550, 581, 584, 585, 587

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 248 (showing top): GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_LIPID_HOMEOSTASIS, GOBP_RESPONSE_TO_STEROL, MODULE_206, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_CHOLESTEROL, GOBP_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_STEROL, GOBP_CELLULAR_RESPONSE_TO_ALCOHOL, GOBP_STEROL_TRANSPORT, GOBP_INTRACELLULAR_LIPID_TRANSPORT, MODULE_397

GO Biological Process (5): intracellular sterol transport (GO:0032366), cholesterol homeostasis (GO:0042632), cellular response to cholesterol (GO:0071397), lipid transport (GO:0006869), sterol transport (GO:0015918)

GO Molecular Function (5): phosphatidylserine binding (GO:0001786), cholesterol binding (GO:0015485), phosphatidic acid binding (GO:0070300), cholesterol transfer activity (GO:0120020), lipid binding (GO:0008289)

GO Cellular Component (7): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), endoplasmic reticulum-plasma membrane contact site (GO:0140268), endoplasmic reticulum (GO:0005783), organelle (GO:0043226), organelle membrane contact site (GO:0044232)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phospholipid binding	2
anion binding	2
intracellular anatomical structure	1
sterol transport	1
intracellular lipid transport	1
sterol homeostasis	1
cellular response to sterol	1
response to cholesterol	1
cellular response to alcohol	1
transport	1
lipid localization	1
lipid transport	1
organic hydroxy compound transport	1
modified amino acid binding	1
sterol binding	1
alcohol binding	1
cholesterol binding	1
sterol transfer activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
organelle membrane contact site	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle	1

Protein interactions and networks

STRING

750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRAMD1B	NPC1	O15118	809
GRAMD1B	STARD3	Q14849	579
GRAMD1B	OSBPL5	Q9H0X9	533
GRAMD1B	HMX2	A2RU54	480
GRAMD1B	OSBP	P22059	478
GRAMD1B	GARNL3	Q5VVW2	462
GRAMD1B	HMX3	A6NHT5	440
GRAMD1B	CARNMT1	Q8N4J0	425
GRAMD1B	TBRG1	Q3YBR2	421
GRAMD1B	PDZD8	Q8NEN9	419
GRAMD1B	OSBPL9	Q96SU4	404
GRAMD1B	MOSPD2	Q8NHP6	393
GRAMD1B	UFSP1	Q6NVU6	392
GRAMD1B	NPC2	P61916	377
GRAMD1B	NXPH2	O95156	372

IntAct

28 interactions, top by confidence:

A	B	Type	Score
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
GRAMD2B	EFCAB14	psi-mi:“MI:0914”(association)	0.530
TNFSF13B	HEATR1	psi-mi:“MI:0914”(association)	0.350
CSNK2A1	EIF3F	psi-mi:“MI:0914”(association)	0.350
COPZ1	ATL3	psi-mi:“MI:0914”(association)	0.350
CSNK2A1	RPS3A	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	VWA8	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
PCDHGB4	FAM171A2	psi-mi:“MI:0914”(association)	0.350
LSMEM2	PCDH17	psi-mi:“MI:0914”(association)	0.350
ANKRD50	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
CTXN1	ABCC4	psi-mi:“MI:0914”(association)	0.350
HTR3A	EXTL3	psi-mi:“MI:0914”(association)	0.350
GRAMD1B	ADD2	psi-mi:“MI:0914”(association)	0.350
EXT1	ZP2	psi-mi:“MI:0914”(association)	0.350
GRAMD1B	TRAPPC10	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
GRAMD1B	MYCBP2	psi-mi:“MI:0914”(association)	0.350
SLC44A4	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC4A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC9A3	ESYT3	psi-mi:“MI:0914”(association)	0.350
STYK1	FAM171A2	psi-mi:“MI:2364”(proximity)	0.270
CELF1	GRAMD1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (112): GRAMD1B (Affinity Capture-MS), GRAMD1B (Affinity Capture-MS), GRAMD1C (Affinity Capture-MS), ZBTB1 (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GTPBP2 (Affinity Capture-MS), PDCD2L (Affinity Capture-MS), GRAMD1B (Affinity Capture-MS), C7orf43 (Affinity Capture-MS), CEP55 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), GRAMD1B (Affinity Capture-MS), TRAPPC10 (Affinity Capture-MS), GRAMD1B (Affinity Capture-MS), GRAMD1B (Affinity Capture-MS)

ESM2 similar proteins: A1A5G2, A2AFR3, A7MBL8, B9EJ86, E1C1R4, E1C3P4, F1LXF1, O94806, O94967, P0C6S7, P0CAX5, P11274, P22682, Q0V9G5, Q14161, Q14CM0, Q15139, Q16513, Q1RMU2, Q3KR37, Q3LAC4, Q3UGM2, Q5RED8, Q5T6S3, Q5U252, Q62101, Q66H62, Q6DFZ1, Q6P5G6, Q6PAJ1, Q70Z35, Q7Z6G8, Q80TI0, Q80TQ2, Q80YA9, Q8BIZ1, Q8BWW9, Q8BY87, Q8K1Y2, Q8NEL9

Diamond homologs: A1CFB3, A1CYS1, A2QNQ5, A7A179, A7ERM5, A7KAK6, A7KAN4, A7TF84, C4B4E5, I1S8Q3, P0CN90, P0CN91, Q00IB7, Q06321, Q08001, Q0CKU4, Q0UY53, Q2U0C3, Q3KR37, Q3KR56, Q4WID6, Q54IL5, Q5A950, Q5B4C9, Q5RC33, Q6BN88, Q6C8M8, Q6CUV2, Q751Z4, Q7S1I0, Q80TI0, Q80TI1, Q8CI52, Q8IYS0, Q8N4B1, Q8NJS1, Q8VEF1, Q96CP6, Q9M8Z7, Q9ULM0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	80
Likely benign	13
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
996583	NM_001387025.1(GRAMD1B):c.811C>T (p.Arg271Ter)	Likely pathogenic

SpliceAI

3780 predictions. Top by Δscore:

Variant	Effect	Δscore
11:123577335:ACCCC:A	acceptor_gain	1.0000
11:123577336:C:G	acceptor_gain	1.0000
11:123577359:C:A	acceptor_gain	1.0000
11:123577364:CAGC:C	acceptor_loss	1.0000
11:123577365:A:T	acceptor_loss	1.0000
11:123577366:G:GA	acceptor_gain	1.0000
11:123577366:GC:G	acceptor_gain	1.0000
11:123577366:GCA:G	acceptor_gain	1.0000
11:123577366:GCACT:G	acceptor_gain	1.0000
11:123577578:GTG:G	donor_loss	1.0000
11:123577579:T:G	donor_loss	1.0000
11:123584333:G:GG	donor_gain	1.0000
11:123593775:G:GT	donor_gain	1.0000
11:123594163:GTTG:G	donor_gain	1.0000
11:123594167:G:C	donor_loss	1.0000
11:123594167:G:GG	donor_gain	1.0000
11:123594168:T:A	donor_loss	1.0000
11:123595913:T:A	acceptor_gain	1.0000
11:123595924:T:TA	acceptor_gain	1.0000
11:123595932:T:TA	acceptor_gain	1.0000
11:123595933:G:A	acceptor_gain	1.0000
11:123596034:AAAGG:A	donor_loss	1.0000
11:123596035:AAGGT:A	donor_loss	1.0000
11:123596038:G:C	donor_loss	1.0000
11:123596039:T:A	donor_loss	1.0000
11:123600461:A:AG	acceptor_gain	1.0000
11:123600462:A:G	acceptor_gain	1.0000
11:123600464:CTAGC:C	acceptor_loss	1.0000
11:123600465:TA:T	acceptor_loss	1.0000
11:123600466:A:AG	acceptor_gain	1.0000

AlphaMissense

5833 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:123594097:T:A	Y91N	1.000
11:123594097:T:C	Y91H	1.000
11:123594097:T:G	Y91D	1.000
11:123594098:A:G	Y91C	1.000
11:123594100:A:G	K92E	1.000
11:123594102:G:C	K92N	1.000
11:123594102:G:T	K92N	1.000
11:123594107:G:C	R94T	1.000
11:123594107:G:T	R94I	1.000
11:123594108:A:C	R94S	1.000
11:123594108:A:T	R94S	1.000
11:123594119:T:C	F98S	1.000
11:123594130:T:A	F102I	1.000
11:123594130:T:C	F102L	1.000
11:123594131:T:C	F102S	1.000
11:123594132:T:A	F102L	1.000
11:123594132:T:G	F102L	1.000
11:123594154:C:A	R110S	1.000
11:123594158:T:A	L111H	1.000
11:123594158:T:C	L111P	1.000
11:123594158:T:G	L111R	1.000
11:123594161:T:A	I112N	1.000
11:123594166:G:C	D114H	1.000
11:123594743:T:C	C117R	1.000
11:123594744:G:A	C117Y	1.000
11:123594744:G:T	C117F	1.000
11:123594745:T:G	C117W	1.000
11:123594746:G:C	A118P	1.000
11:123594747:C:A	A118E	1.000
11:123594747:C:T	A118V	1.000

dbSNP variants (sampled 300 via entrez): RS1000022240 (11:123448531 T>C), RS1000028651 (11:123380500 A>G), RS1000048949 (11:123526385 CG>C), RS1000053200 (11:123448238 C>G), RS1000054617 (11:123508520 A>G), RS1000057477 (11:123591759 C>T), RS1000058169 (11:123380796 C>A), RS1000075017 (11:123467251 G>A), RS1000087713 (11:123548649 C>T), RS1000096030 (11:123387316 C>T), RS1000101635 (11:123530438 C>A,T), RS1000114456 (11:123620762 C>T), RS1000117779 (11:123599933 T>C), RS1000137782 (11:123426076 C>A,T), RS1000145974 (11:123608763 C>T)

Disease associations

OMIM: gene MIM:620179 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

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

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000224_4	Chronic lymphocytic leukemia	4.000000e-12
GCST002299_15	Chronic lymphocytic leukemia	4.000000e-24
GCST002539_9	Schizophrenia	8.000000e-09
GCST003468_13	Chronic lymphocytic leukemia	2.000000e-40
GCST003960_4	Ulcerative colitis	6.000000e-06
GCST004099_7	B-cell malignancies (chronic lymphocytic leukemia, Hodgkin lymphoma or multiple myeloma) (pleiotropy)	3.000000e-14
GCST004146_16	Chronic lymphocytic leukemia	4.000000e-58
GCST004946_40	Schizophrenia	1.000000e-09
GCST005082_5	Bipolar disorder lithium response (categorical) or schizophrenia	5.000000e-08
GCST005761_1	Immunoglobulin M against phosphorylcholine (IgM anti-PC) levels	4.000000e-11
GCST006803_45	Schizophrenia	5.000000e-08
GCST007017_15	Serum bilirubin levels x Mediterranean diet adherence interaction in metabolic syndrome	8.000000e-06
GCST007201_125	Schizophrenia	1.000000e-10
GCST007201_436	Schizophrenia	1.000000e-07
GCST008514_17	Peginterferon alfa-2a treatment response in chronic hepatitis B infection	8.000000e-06
GCST008575_2	IgM levels	1.000000e-23
GCST010002_200	Refractive error	5.000000e-21
GCST012490_382	Femur bone mineral density x serum urate levels interaction	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement
EFO:0008111	diet measurement
EFO:0010103	response to peginterferon alfa-2a
EFO:0004531	urate measurement

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)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs61123830	Efficacy	3	lithium	Bipolar Disorder

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs61123830	GRAMD1B	3	0.00	1	lithium

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Estradiol	increases expression, affects cotreatment	2
mivebresib	decreases expression	1
sotorasib	decreases expression, affects cotreatment	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
trichostatin A	decreases expression	1
dodecyldimethylamine oxide	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
didecyldimethylammonium	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Acrolein	increases abundance, affects cotreatment, decreases expression	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1

Clinical trials (associated diseases)

197 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)
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
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders