GRAMD1A

Summary

GRAMD1A (GRAM domain containing 1A, HGNC:29305) is a protein-coding gene on chromosome 19q13.11, encoding Protein Aster-A (Q96CP6). 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 and cholesterol transfer activity. Predicted to be involved in cellular response to cholesterol and intracellular sterol transport. Located in several cellular components, including cytosol; endoplasmic reticulum membrane; and organelle membrane contact site.

Source: NCBI Gene 57655 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 134 total
• Druggable target: yes
• MANE Select transcript: NM_020895

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29305
Approved symbol	GRAMD1A
Name	GRAM domain containing 1A
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	LAMa, FLJ90346
Ensembl gene	ENSG00000089351
Ensembl biotype	protein_coding
OMIM	620178
Entrez	57655

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 18 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000317991, ENST00000411896, ENST00000424536, ENST00000594597, ENST00000595596, ENST00000598073, ENST00000598118, ENST00000598362, ENST00000598580, ENST00000599476, ENST00000599564, ENST00000600231, ENST00000603669, ENST00000603907, ENST00000680623, ENST00000940004, ENST00000940005, ENST00000940006, ENST00000942865, ENST00000942866, ENST00000942867, ENST00000942868, ENST00000942869, ENST00000942870, ENST00000942871, ENST00000942872, ENST00000942873, ENST00000942874

RefSeq mRNA: 5 — MANE Select: NM_020895 NM_001136199, NM_001320034, NM_001320035, NM_001320036, NM_020895

CCDS: CCDS42546, CCDS46046, CCDS92585

Canonical transcript exons

ENST00000317991 — 20 exons

Exon	Start	End
ENSE00002206381	35013256	35013368
ENSE00002519772	35022900	35022911
ENSE00003463274	35010284	35010379
ENSE00003474128	35010092	35010195
ENSE00003474172	35021951	35022038
ENSE00003480543	35009423	35009443
ENSE00003482635	35000323	35000486
ENSE00003520609	35021502	35021605
ENSE00003567080	35021691	35021864
ENSE00003572755	35023427	35023547
ENSE00003595807	35011474	35011554
ENSE00003600660	35009119	35009329
ENSE00003615877	35019191	35019309
ENSE00003622575	35009888	35009972
ENSE00003629842	35019391	35019533
ENSE00003644103	35026049	35026469
ENSE00003650985	35015824	35015967
ENSE00003680654	35014189	35014387
ENSE00003680960	35023236	35023343
ENSE00003682748	35013541	35013691

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.2440 / max 646.9706, expressed in 1815 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175174	35.5534	1812
175175	5.3830	1284
175177	0.9919	448
175179	0.5696	133
175176	0.5300	304
175178	0.0831	37
175169	0.0518	12
175171	0.0321	9
175167	0.0276	6
175168	0.0159	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.45	gold quality
upper lobe of left lung	UBERON:0008952	97.25	gold quality
right uterine tube	UBERON:0001302	96.93	gold quality
left uterine tube	UBERON:0001303	96.62	gold quality
endocervix	UBERON:0000458	96.60	gold quality
left ovary	UBERON:0002119	96.58	gold quality
right ovary	UBERON:0002118	96.42	gold quality
mucosa of stomach	UBERON:0001199	96.36	gold quality
vermiform appendix	UBERON:0001154	96.15	gold quality
right lung	UBERON:0002167	96.03	gold quality
upper lobe of lung	UBERON:0008948	95.73	gold quality
cortical plate	UBERON:0005343	95.72	gold quality
body of uterus	UBERON:0009853	95.66	gold quality
omental fat pad	UBERON:0010414	95.42	gold quality
peritoneum	UBERON:0002358	95.35	gold quality
right adrenal gland	UBERON:0001233	95.32	gold quality
body of stomach	UBERON:0001161	95.31	gold quality
right adrenal gland cortex	UBERON:0035827	95.28	gold quality
spleen	UBERON:0002106	95.20	gold quality
left adrenal gland cortex	UBERON:0035825	95.18	gold quality
left adrenal gland	UBERON:0001234	95.14	gold quality
granulocyte	CL:0000094	95.07	gold quality
tibial nerve	UBERON:0001323	95.03	gold quality
ganglionic eminence	UBERON:0004023	94.89	gold quality
apex of heart	UBERON:0002098	94.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.73	gold quality
pancreas	UBERON:0001264	94.66	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.62	gold quality
lower esophagus	UBERON:0013473	94.58	gold quality
right lobe of thyroid gland	UBERON:0001119	94.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-70580	yes	246.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting GRAMD1A, 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-1468-3P	99.96	72.74	3797
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4669	97.94	62.71	224
HSA-MIR-5699-5P	97.36	67.03	1014
HSA-MIR-4750-3P	96.65	64.38	512
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-4256	96.22	67.70	669
HSA-MIR-11181-5P	96.12	67.46	665
HSA-MIR-6075	93.03	64.73	45
HSA-MIR-10392-3P	88.79	61.83	122
HSA-MIR-6070	86.37	66.56	59

Literature-anchored findings (GeneRIF, showing 3)

• STAT5 was the target of GRAMD1A; GRAMD1A regulated the target genes of STAT5 and the transcriptional activity of STAT5. Inhibition of STAT5 in indicated HCC cells overexpressing GRAMD1A suppressed the effects of GRAMD1A on the self-renewal of HCC stem cell, resistance to chemotherapy and tumor growth, suggesting GRAMD1A promoted the self-renewal of HCC stem cells and the development of HCC by increasing STAT5 level. (PMID:27585821)
• GRAMD2a, but not GRAMD1a, co-localizes with the E-Syt2/3 tethers at endoplasmic reticulum-plasma membrane contact sites in a phosphatidylinositol phosphate lipid-dependent manner. Data from an analysis of cells lacking GRAMD2a suggest that it is an organizer of the membrane contact sites with pleiotropic functions including calcium homeostasis. (PMID:29469807)
• GRAMD1A Is a Biomarker of Kidney Renal Clear Cell Carcinoma and Is Associated with Immune Infiltration in the Tumour Microenvironment. (PMID:35860689)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gramd1a	ENSDARG00000076689
mus_musculus	Gramd1a	ENSMUSG00000001248
rattus_norvegicus	Gramd1a	ENSRNOG00000021106
drosophila_melanogaster	GramD1B	FBGN0085423
caenorhabditis_elegans	ZC328.3	WBGENE00022593

Paralogs (4): GRAMD1B (ENSG00000023171), GRAMD2B (ENSG00000155324), GRAMD2A (ENSG00000175318), GRAMD1C (ENSG00000178075)

Protein

Protein identifiers

Protein Aster-A — Q96CP6 (reviewed: Q96CP6)

Alternative names: GRAM domain-containing protein 1A

All UniProt accessions (4): Q96CP6, M0QZ12, M0R0J9, S4R3I2

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 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. May play a role in tumor progression. Plays a role in autophagy regulation and is required for biogenesis of the autophagosome. This function in autophagy requires its cholesterol-transfer activity.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane. Cytoplasmic vesicle. Autophagosome.

Tissue specificity. Expressed in liver.

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.

Induction. Up-regulated in hepatocellular carcinoma tissues.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96CP6-1	1	yes
Q96CP6-2	2
Q96CP6-3	3

RefSeq proteins (5): NP_001129671, NP_001306963, NP_001306964, NP_001306965, NP_065946* (*=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 (20 total): compositionally biased region 5, modified residue 4, region of interest 3, splice variant 2, sequence conflict 2, domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CP6-F1	68.70	0.33

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 (4): 263, 267, 271, 415

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 193 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_CELLULAR_RESPONSE_TO_LIPID, TGCACTT_MIR519C_MIR519B_MIR519A, MODULE_522, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, PATIL_LIVER_CANCER, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_RESPONSE_TO_STEROL, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_CHOLESTEROL, LIAO_METASTASIS, GOBP_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_STEROL

GO Biological Process (4): autophagy (GO:0006914), intracellular sterol transport (GO:0032366), cellular response to cholesterol (GO:0071397), lipid transport (GO:0006869)

GO Molecular Function (4): cholesterol binding (GO:0015485), cholesterol transfer activity (GO:0120020), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (9): autophagosome (GO:0005776), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), organelle membrane contact site (GO:0044232), endoplasmic reticulum-plasma membrane contact site (GO:0140268), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	3
binding	2
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
intracellular anatomical structure	1
sterol transport	1
intracellular lipid transport	1
cellular response to sterol	1
response to cholesterol	1
cellular response to alcohol	1
transport	1
lipid localization	1
sterol binding	1
alcohol binding	1
cholesterol binding	1
sterol transfer activity	1
vacuole	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
intracellular vesicle	1
organelle	1
organelle membrane contact site	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRAMD1A	ESYT3	A0FGR9	540
GRAMD1A	RBM42	Q9BTD8	516
GRAMD1A	ESYT1	Q9BSJ8	499
GRAMD1A	STARD3	Q14849	462
GRAMD1A	OSBPL5	Q9H0X9	461
GRAMD1A	SKIC3	Q6PGP7	443
GRAMD1A	VPS13A	Q96RL7	435
GRAMD1A	PCTP	Q9UKL6	430
GRAMD1A	OSBPL8	Q9BZF1	412
GRAMD1A	OSBP	P22059	412
GRAMD1A	HAUS5	O94927	409
GRAMD1A	CHSY3	Q70JA7	408
GRAMD1A	ESYT2	A0FGR8	404
GRAMD1A	CERT1	Q9Y5P4	393
GRAMD1A	RALGAPA1	Q6GYQ0	391

IntAct

126 interactions, top by confidence:

A	B	Type	Score
RPS6KA3	ROCK2	psi-mi:“MI:0914”(association)	0.640
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
FLJ13057	GRAMD1A	psi-mi:“MI:0915”(physical association)	0.560
MAL	GRAMD1A	psi-mi:“MI:0915”(physical association)	0.560
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
GRAMD2B	EFCAB14	psi-mi:“MI:0914”(association)	0.530
ACVR1	BMPR1A	psi-mi:“MI:0914”(association)	0.530
PKD2L2	PKD2	psi-mi:“MI:0914”(association)	0.530
TMX1	PLXNB2	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
GRAMD1A	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
CALML6	GRAMD1A	psi-mi:“MI:0915”(physical association)	0.400
GRAMD1A	CCR1	psi-mi:“MI:0915”(physical association)	0.370
GRAMD1A	TLR7	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
CD74		psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
TNFSF13B	HEATR1	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (242): GMCL1 (Two-hybrid), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), GRAMD1A (Proximity Label-MS), GRAMD1A (Proximity Label-MS), GRAMD1A (Proximity Label-MS)

ESM2 similar proteins: A1A4I4, A1A5B6, A4D2P6, B2DCZ9, B4F7F3, O00192, O08773, O08874, O08908, O35465, O43566, O62683, O75808, O95049, P70268, P97492, Q0QWG9, Q12851, Q14164, Q14318, Q16512, Q16513, Q3B7U9, Q3KR56, Q3MII6, Q3UFB7, Q5FVC2, Q60875, Q61161, Q63433, Q63788, Q6P5Z2, Q6PFQ7, Q6V7V2, Q6ZT62, Q7Z5H3, Q865S3, Q8BWW9, Q8IYK8, Q8K045

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 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
Synthesis of PC	5	18.2×	3e-04
R-HSA-425393	12	13.9×	2e-08
Neurotransmitter receptors and postsynaptic signal transmission	12	10.7×	2e-07
Transmission across Chemical Synapses	12	8.2×	3e-06
SLC-mediated transmembrane transport	14	7.4×	8e-07
COPI-dependent Golgi-to-ER retrograde traffic	7	6.9×	2e-03
Neuronal System	13	5.1×	7e-05
Transport of small molecules	19	4.3×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of intracellular pH	8	34.4×	5e-08
synaptic transmission, cholinergic	5	28.7×	9e-05
acetylcholine receptor signaling pathway	6	26.8×	2e-05
intra-Golgi vesicle-mediated transport	6	22.6×	4e-05
sodium ion import across plasma membrane	5	22.3×	2e-04
membrane depolarization	6	21.9×	5e-05
monoatomic ion transport	12	13.4×	5e-08
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	5	12.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2943 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35000485:GA:G	donor_gain	1.0000
19:35000487:G:GG	donor_gain	1.0000
19:35009110:T:TA	acceptor_gain	1.0000
19:35009114:CCCAG:C	acceptor_loss	1.0000
19:35009116:CAGCA:C	acceptor_loss	1.0000
19:35009117:A:AG	acceptor_gain	1.0000
19:35009117:A:T	acceptor_loss	1.0000
19:35009118:G:GA	acceptor_gain	1.0000
19:35009118:GC:G	acceptor_gain	1.0000
19:35009118:GCA:G	acceptor_gain	1.0000
19:35009118:GCAC:G	acceptor_gain	1.0000
19:35009118:GCACC:G	acceptor_gain	1.0000
19:35009325:GCAAG:G	donor_gain	1.0000
19:35009330:GTT:G	donor_loss	1.0000
19:35009421:A:AG	acceptor_gain	1.0000
19:35009422:G:GG	acceptor_gain	1.0000
19:35009884:TCAG:T	acceptor_loss	1.0000
19:35009885:CAGAT:C	acceptor_loss	1.0000
19:35009886:A:AG	acceptor_gain	1.0000
19:35009886:A:AT	acceptor_loss	1.0000
19:35009887:G:GA	acceptor_gain	1.0000
19:35009887:GA:G	acceptor_gain	1.0000
19:35009887:GAT:G	acceptor_gain	1.0000
19:35009969:GTGG:G	donor_gain	1.0000
19:35009970:TGGG:T	donor_loss	1.0000
19:35009971:GG:G	donor_gain	1.0000
19:35009972:GG:G	donor_gain	1.0000
19:35009973:G:GG	donor_gain	1.0000
19:35009973:GT:G	donor_loss	1.0000
19:35009974:T:G	donor_loss	1.0000

AlphaMissense

4713 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35009903:T:C	Y86H	1.000
19:35009903:T:G	Y86D	1.000
19:35009912:C:A	R89S	1.000
19:35009913:G:C	R89P	1.000
19:35009925:T:C	F93S	1.000
19:35009936:T:C	F97L	1.000
19:35009938:C:A	F97L	1.000
19:35009938:C:G	F97L	1.000
19:35009964:T:C	L106P	1.000
19:35010100:T:C	C112R	1.000
19:35010101:G:A	C112Y	1.000
19:35010102:C:G	C112W	1.000
19:35010104:C:A	A113D	1.000
19:35010107:T:C	L114P	1.000
19:35010119:T:A	I118N	1.000
19:35010119:T:C	I118T	1.000
19:35010119:T:G	I118S	1.000
19:35010122:T:A	L119Q	1.000
19:35010122:T:C	L119P	1.000
19:35010122:T:G	L119R	1.000
19:35010125:T:C	L120P	1.000
19:35010130:G:A	G122S	1.000
19:35010130:G:C	G122R	1.000
19:35010130:G:T	G122C	1.000
19:35010131:G:A	G122D	1.000
19:35010131:G:C	G122A	1.000
19:35010131:G:T	G122V	1.000
19:35010133:C:A	R123S	1.000
19:35010134:G:C	R123P	1.000
19:35010137:T:C	L124P	1.000

dbSNP variants (sampled 300 via entrez): RS1000017153 (19:35002660 C>A), RS1000093038 (19:35004217 C>T), RS1000167249 (19:35024004 C>A,G), RS1000207779 (19:35023774 G>A,T), RS1000211295 (19:35020227 A>G), RS1000311554 (19:35025177 A>G), RS1000325215 (19:35008827 A>G), RS1000386372 (19:35013847 G>A,C), RS1000548740 (19:35021333 G>A), RS1000651422 (19:35017607 C>G), RS1000695492 (19:35026202 C>T), RS1000717671 (19:35018907 G>A), RS1000723619 (19:35012759 G>A), RS1000755245 (19:35012534 C>G,T), RS1000968165 (19:35005066 G>A)

Disease associations

OMIM: gene MIM:620178 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003901_15	Cognitive decline (age-related)	4.000000e-06
GCST006993_14	Hippocampal volume in Alzheimer’s disease dementia	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5725017 (SINGLE PROTEIN), CHEMBL6066028 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

21 potent at pChembl≥5 of 23 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.43	Kd	37	nM	CHEMBL5568818
7.31	Kd	49	nM	CHEMBL5591294
7.17	Kd	68	nM	CHEMBL5565997
7.08	Kd	83	nM	CHEMBL5574895
7.07	Kd	86	nM	CHEMBL5565997
7.06	Kd	88	nM	CHEMBL5591294
7.05	Kd	90	nM	CHEMBL5574895
6.96	Kd	110	nM	CHEMBL5568818
6.83	Kd	149	nM	CHEMBL5562524
6.38	Kd	421.5	nM	CHEMBL5653589
6.30	ED50	494.9	nM	CHEMBL5653589
6.13	Kd	745	nM	CHEMBL5566257
6.12	Kd	765	nM	CHEMBL5566257
5.94	IC50	1155	nM	CHEMBL2354929
5.93	IC50	1181	nM	CHEMBL5589956
5.83	IC50	1470	nM	CHEMBL5573661
5.74	IC50	1842	nM	CHEMBL2354929
5.71	IC50	1930	nM	CHEMBL5589956
5.56	IC50	2753	nM	CHEMBL5566774
5.43	IC50	3697	nM	CHEMBL5573661
5.33	IC50	4677	nM	CHEMBL5566774

PubChem BioAssay actives

20 with measured affinity, of 57 total; 11 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
tert-butyl 2-[[4-[3-[2-[3-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]propoxy]ethoxy]propylcarbamoyl]benzoyl]amino]-4,6,7,7a-tetrahydro-3aH-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107475: Binding affinity to aster A (unknown origin) by fluorescence polarization method	kd	0.0370	uM
tert-butyl 2-[[4-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]benzoyl]amino]-4,6,7,7a-tetrahydro-3aH-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107475: Binding affinity to aster A (unknown origin) by fluorescence polarization method	kd	0.0490	uM
tert-butyl 2-[[4-[3-[2-[2-[3-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]propoxy]ethoxy]ethoxy]propylcarbamoyl]benzoyl]amino]-4,6,7,7a-tetrahydro-3aH-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107475: Binding affinity to aster A (unknown origin) by fluorescence polarization method	kd	0.0680	uM
tert-butyl 2-[[4-[3-[4-[3-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]propoxy]butoxy]propylcarbamoyl]benzoyl]amino]-4,6,7,7a-tetrahydro-3aH-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107474: Binding affinity to aster A (unknown origin) assessed as change in fluorescence intensity	kd	0.0830	uM
tert-butyl 2-[[4-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethylcarbamoyl]benzoyl]amino]-4,6,7,7a-tetrahydro-3aH-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107475: Binding affinity to aster A (unknown origin) by fluorescence polarization method	kd	0.1490	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148459: Binding affinity to human GRAMD1A incubated for 45 mins by Kinobead based pull down assay	kd	0.4215	uM
tert-butyl 2-[[4-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexylcarbamoyl]benzoyl]amino]-4,6,7,7a-tetrahydro-3aH-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107475: Binding affinity to aster A (unknown origin) by fluorescence polarization method	kd	0.7450	uM
(3S,8R,9S,10R,13S,14S)-3-[2-(diethylamino)ethoxy]-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one;hydrochloride	2107477: Displacement of tert-butyl 2-(4-((3-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propoxy)butoxy)propyl)carbamoyl)benzamido)-3a,6,7,7a-tetrahydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate from aster A (unknown origin) assessed as change in fluorescence intensity	ic50	1.1550	uM
tert-butyl 2-[(4-propan-2-yloxybenzoyl)amino]-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107477: Displacement of tert-butyl 2-(4-((3-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propoxy)butoxy)propyl)carbamoyl)benzamido)-3a,6,7,7a-tetrahydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate from aster A (unknown origin) assessed as change in fluorescence intensity	ic50	1.1810	uM
tert-butyl 2-[[4-[2-[2-[2-[[(2S)-1-[(2R,4S)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylcarbamoyl]benzoyl]amino]-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107477: Displacement of tert-butyl 2-(4-((3-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propoxy)butoxy)propyl)carbamoyl)benzamido)-3a,6,7,7a-tetrahydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate from aster A (unknown origin) assessed as change in fluorescence intensity	ic50	1.4700	uM
tert-butyl 2-[[4-[[7-[[(2S)-1-[(2R,4S)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-7-oxoheptyl]carbamoyl]benzoyl]amino]-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate	2107477: Displacement of tert-butyl 2-(4-((3-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propoxy)butoxy)propyl)carbamoyl)benzamido)-3a,6,7,7a-tetrahydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate from aster A (unknown origin) assessed as change in fluorescence intensity	ic50	2.7530	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Copper	affects binding, increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Disulfiram	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5550801	Binding	Binding affinity to aster A (unknown origin) assessed as change in fluorescence intensity	Fluorescent probes and degraders of the sterol transport protein Aster-A. — Bioorg Med Chem

Clinical trials (associated diseases)

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