GRAMD2B

Summary

GRAMD2B (GRAM domain containing 2B, HGNC:24911) is a protein-coding gene on chromosome 5q23.2, encoding GRAM domain-containing protein 2B (Q96HH9).

Enables identical protein binding activity. Located in cytoplasmic microtubule.

Source: NCBI Gene 65983 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 74 total — 1 pathogenic
• MANE Select transcript: NM_023927

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24911
Approved symbol	GRAMD2B
Name	GRAM domain containing 2B
Location	5q23.2
Locus type	gene with protein product
Status	Approved
Aliases	NS3TP2, FLJ21313
Ensembl gene	ENSG00000155324
Ensembl biotype	protein_coding
OMIM	620182
Entrez	65983

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 14 protein_coding, 6 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000285689, ENST00000502348, ENST00000503702, ENST00000504859, ENST00000505441, ENST00000505720, ENST00000506445, ENST00000508523, ENST00000509882, ENST00000511134, ENST00000512579, ENST00000513040, ENST00000513913, ENST00000513978, ENST00000514099, ENST00000514932, ENST00000515200, ENST00000542322, ENST00000544396, ENST00000880471, ENST00000880472, ENST00000880473, ENST00000921003, ENST00000971358, ENST00000971359

RefSeq mRNA: 9 — MANE Select: NM_023927 NM_001146319, NM_001146320, NM_001146321, NM_001146322, NM_001349541, NM_001349542, NM_001349543, NM_001349544, NM_023927

CCDS: CCDS4136, CCDS54891, CCDS54892, CCDS54893, CCDS54894

Canonical transcript exons

ENST00000285689 — 14 exons

Exon	Start	End
ENSE00003476534	126488799	126488892
ENSE00003483617	126480456	126480527
ENSE00003516811	126484402	126484524
ENSE00003521306	126483463	126483574
ENSE00003548430	126472238	126472304
ENSE00003549040	126480627	126480707
ENSE00003565225	126486873	126486977
ENSE00003603345	126485686	126485773
ENSE00003623250	126465426	126465545
ENSE00003627144	126469677	126469788
ENSE00003631851	126477692	126477787
ENSE00003661636	126473265	126473368
ENSE00003891750	126423409	126423689
ENSE00003891959	126492915	126494364

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.0519 / max 426.5635, expressed in 1743 samples.

FANTOM5 promoters (28 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58279	16.5743	1666
58280	5.1313	1240
58273	1.3319	735
58270	0.7106	115
58281	0.6434	320
58272	0.5015	231
58282	0.4953	243
58278	0.4849	233
58277	0.4240	172
58284	0.2800	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.62	gold quality
medial globus pallidus	UBERON:0002477	97.69	gold quality
globus pallidus	UBERON:0001875	97.49	gold quality
corpus callosum	UBERON:0002336	97.49	gold quality
lateral globus pallidus	UBERON:0002476	97.12	gold quality
bronchial epithelial cell	CL:0002328	96.64	gold quality
decidua	UBERON:0002450	96.06	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.32	gold quality
epithelium of bronchus	UBERON:0002031	95.17	gold quality
bronchus	UBERON:0002185	95.10	gold quality
jejunal mucosa	UBERON:0000399	94.88	gold quality
choroid plexus epithelium	UBERON:0003911	94.68	gold quality
placenta	UBERON:0001987	94.41	gold quality
caudate nucleus	UBERON:0001873	94.34	gold quality
superior vestibular nucleus	UBERON:0007227	94.17	gold quality
amygdala	UBERON:0001876	94.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.01	gold quality
medulla oblongata	UBERON:0001896	93.86	gold quality
subthalamic nucleus	UBERON:0001906	93.79	gold quality
putamen	UBERON:0001874	93.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.70	gold quality
buccal mucosa cell	CL:0002336	93.65	silver quality
right uterine tube	UBERON:0001302	93.59	gold quality
trachea	UBERON:0003126	93.40	gold quality
cranial nerve II	UBERON:0000941	93.27	gold quality
sural nerve	UBERON:0015488	93.15	gold quality
endometrium	UBERON:0001295	93.11	gold quality
thyroid gland	UBERON:0002046	93.09	gold quality
blood vessel layer	UBERON:0004797	92.91	gold quality
seminal vesicle	UBERON:0000998	92.87	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	1670.88
E-HCAD-35	yes	73.92
E-HCAD-25	yes	24.07
E-GEOD-84465	yes	12.16
E-MTAB-6075	no	295.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting GRAMD2B, 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-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4487	99.96	64.58	1252
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gramd2b	ENSMUSG00000001700
rattus_norvegicus	Gramd2b	ENSRNOG00000015225
drosophila_melanogaster	GramD1B	FBGN0085423
caenorhabditis_elegans	ZC328.3	WBGENE00022593

Paralogs (4): GRAMD1B (ENSG00000023171), GRAMD1A (ENSG00000089351), GRAMD2A (ENSG00000175318), GRAMD1C (ENSG00000178075)

Protein

Protein identifiers

GRAM domain-containing protein 2B — Q96HH9 (reviewed: Q96HH9)

Alternative names: HCV NS3-transactivated protein 2

All UniProt accessions (6): Q96HH9, B7Z4W8, D6R9P9, D6REP5, D6RFH3, E9PD09

Isoforms (5)

UniProt ID	Names	Canonical?
Q96HH9-1	1	yes
Q96HH9-2	2
Q96HH9-3	3
Q96HH9-4	4
Q96HH9-5	5

RefSeq proteins (9): NP_001139791, NP_001139792, NP_001139793, NP_001139794, NP_001336470, NP_001336471, NP_001336472, NP_001336473, NP_076416* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004182	GRAM	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR052633	GRAM_domain_protein_2B	Family

Pfam: PF02893

UniProt features (20 total): splice variant 5, modified residue 4, region of interest 4, compositionally biased region 4, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HH9-F1	63.97	0.26

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): 1, 225, 242, 252

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 254 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, ATACCTC_MIR202, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, ABBUD_LIF_SIGNALING_1_UP, ZHAN_MULTIPLE_MYELOMA_CD1_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GAVIN_FOXP3_TARGETS_CLUSTER_P7, SMID_BREAST_CANCER_LUMINAL_B_DN, GOCC_CYTOPLASMIC_MICROTUBULE, BOCHKIS_FOXA2_TARGETS, MATSUDA_NATURAL_KILLER_DIFFERENTIATION, REN_ALVEOLAR_RHABDOMYOSARCOMA_DN

GO Biological Process (0):

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasmic microtubule (GO:0005881), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein binding	1
binding	1
cytoplasm	1
microtubule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRAMD2B	ZNF608	Q9ULD9	546
GRAMD2B	SPMIP10	Q6ZNM6	529
GRAMD2B	PHAX	Q9H814	480
GRAMD2B	MINAR2	P59773	479
GRAMD2B	PHF19	Q5T6S3	420
GRAMD2B	MARCHF3	Q86UD3	404
GRAMD2B	PDXDC1	Q6P996	395
GRAMD2B	ESYT3	A0FGR9	358
GRAMD2B	ATRNL1	Q5VV63	351
GRAMD2B	KCNAB2	Q13303	335
GRAMD2B	PTPRZ1	P23471	328
GRAMD2B	PRELID3B	Q9Y3B1	326
GRAMD2B	C5orf63	A6NC05	314
GRAMD2B	CYBRD1	Q53TN4	313
GRAMD2B	WDR81	Q562E7	313

IntAct

75 interactions, top by confidence:

A	B	Type	Score
PAEP	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.830
GRAMD2B	PAEP	psi-mi:“MI:0915”(physical association)	0.830
GRAMD2B	FRMD8	psi-mi:“MI:0915”(physical association)	0.720
FRMD8	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.720
CD207	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.720
TMEM43	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.720
GRAMD2B	TMEM43	psi-mi:“MI:0915”(physical association)	0.720
GRAMD2B	CD207	psi-mi:“MI:0915”(physical association)	0.720
GRAMD2B	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.670
GRAMD2B	ATG15	psi-mi:“MI:0915”(physical association)	0.610
ATG15	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.610
ABO	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.560
MORF4L2	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.560
NAPRT	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.560
GRAMD2B	ABO	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (88): GRAMD3 (Two-hybrid), GRAMD3 (Two-hybrid), GRAMD3 (Two-hybrid), GRAMD3 (Two-hybrid), GRAMD3 (Two-hybrid), FRMD8 (Two-hybrid), NAPRT (Two-hybrid), GRAMD1B (Affinity Capture-MS), GRAMD1C (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), EFCAB14 (Affinity Capture-MS), TXLNG (Affinity Capture-MS), EXD2 (Affinity Capture-MS), TXLNA (Affinity Capture-MS), GOLM1 (Affinity Capture-MS)

ESM2 similar proteins: A2AD83, A4Q9F0, A6QP06, A7KAX9, B2RYE5, B4K6T8, F7E540, G5EEW9, O00443, O13839, O43283, O96838, P11171, P11434, P48193, Q12923, Q14693, Q22744, Q3V0G7, Q5FVG2, Q5R8N8, Q5R8X7, Q5RAY1, Q61194, Q64512, Q6DTM3, Q6GPD0, Q6Q7P4, Q6ZT98, Q6ZUT3, Q811P8, Q8BGS1, Q8BPQ7, Q8CHB8, Q8K3Y6, Q8WYB5, Q91573, Q91ZP3, Q96HH9, Q99PI5

Diamond homologs: A3KGB4, F4HVW5, O42976, O95759, P38800, P43560, Q06681, Q3KR37, Q3KR56, Q3UYK3, Q3V3G7, Q5FVG8, Q5R8N8, Q5RC33, Q6PEM6, Q6ZT07, Q80TI0, Q8IUY3, Q8IYS0, Q8MVR1, Q8VEF1, Q96CP6, Q96HH9, Q9Z1A9, Q9ZVT9, Q54HC6, Q54IL5, Q5B4C9, Q8CI52, Q8W4D4, Q08001, Q5SVR0, Q66K14, A1CFB3, A2QNQ5, A7KAN4, B0R0W9, C4B4E5, Q0CKU4, Q0IIM8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	48
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1527183	GRCh37/hg19 5q21.1-23.2(chr5:100607918-125900735)	Pathogenic

SpliceAI

2137 predictions. Top by Δscore:

Variant	Effect	Δscore
5:126465424:A:AG	acceptor_gain	1.0000
5:126465425:G:GG	acceptor_gain	1.0000
5:126465425:GCTCA:G	acceptor_gain	1.0000
5:126465541:CTATG:C	donor_gain	1.0000
5:126465542:TATG:T	donor_gain	1.0000
5:126465543:ATGG:A	donor_loss	1.0000
5:126465544:TG:T	donor_gain	1.0000
5:126465544:TGGTA:T	donor_loss	1.0000
5:126465545:GG:G	donor_gain	1.0000
5:126465545:GGT:G	donor_loss	1.0000
5:126465546:G:GG	donor_gain	1.0000
5:126465546:GT:G	donor_loss	1.0000
5:126465547:TAAGT:T	donor_loss	1.0000
5:126466283:T:A	acceptor_gain	1.0000
5:126472236:A:AG	acceptor_gain	1.0000
5:126472237:G:GG	acceptor_gain	1.0000
5:126472300:GCAAA:G	donor_gain	1.0000
5:126472305:G:GG	donor_gain	1.0000
5:126473261:CCA:C	acceptor_loss	1.0000
5:126473262:CAG:C	acceptor_loss	1.0000
5:126473264:G:GT	acceptor_loss	1.0000
5:126477687:TTCA:T	acceptor_loss	1.0000
5:126477690:A:AG	acceptor_gain	1.0000
5:126477690:A:AT	acceptor_loss	1.0000
5:126477691:G:GG	acceptor_gain	1.0000
5:126477691:GAT:G	acceptor_gain	1.0000
5:126477691:GATC:G	acceptor_gain	1.0000
5:126477691:GATCT:G	acceptor_gain	1.0000
5:126477786:GG:G	donor_gain	1.0000
5:126477787:GG:G	donor_gain	1.0000

AlphaMissense

2828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:126473336:T:C	F152L	1.000
5:126473338:T:A	F152L	1.000
5:126473338:T:G	F152L	1.000
5:126473275:T:G	C131W	0.999
5:126473280:T:C	L133P	0.999
5:126473303:G:A	G141R	0.999
5:126473303:G:C	G141R	0.999
5:126473304:G:A	G141E	0.999
5:126473304:G:T	G141V	0.999
5:126473310:T:C	L143P	0.999
5:126473337:T:C	F152S	0.999
5:126477741:C:A	A179D	0.999
5:126477759:C:A	A185D	0.999
5:126472257:T:C	F112S	0.998
5:126473277:C:A	A132D	0.998
5:126473335:T:G	C151W	0.998
5:126473342:T:C	S154P	0.998
5:126477758:G:C	A185P	0.998
5:126477762:T:C	L186P	0.998
5:126480463:T:C	F197S	0.998
5:126472268:T:C	F116L	0.997
5:126472270:T:A	F116L	0.997
5:126472270:T:G	F116L	0.997
5:126473273:T:C	C131R	0.997
5:126473274:G:A	C131Y	0.997
5:126473310:T:A	L143H	0.997
5:126473318:T:C	S146P	0.997
5:126477714:T:A	V170E	0.997
5:126477757:C:A	N184K	0.997
5:126477757:C:G	N184K	0.997

dbSNP variants (sampled 300 via entrez): RS1000011831 (5:126481977 A>G), RS1000014996 (5:126479495 C>G), RS1000072676 (5:126361131 T>C), RS1000078594 (5:126401509 T>C), RS1000105749 (5:126401828 T>C), RS1000116602 (5:126486515 G>A), RS1000143458 (5:126443897 CA>C), RS1000145672 (5:126472616 T>C), RS1000182234 (5:126424168 C>T), RS1000225326 (5:126455199 C>G,T), RS1000240105 (5:126475013 A>G), RS1000245644 (5:126420856 G>A), RS1000324481 (5:126468161 T>C), RS1000335400 (5:126384102 A>C), RS1000366686 (5:126383780 C>T)

Disease associations

OMIM: gene MIM:620182 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000579_62	Cognitive performance	9.000000e-06
GCST001017_15	Diabetic retinopathy	9.000000e-06
GCST006206_1	Thiopurine-induced alopecia in inflammatory bowel disease	5.000000e-07
GCST006533_1	Visceral adipose tissue adjusted for BMI	5.000000e-08
GCST006533_2	Visceral adipose tissue adjusted for BMI	1.000000e-06
GCST006542_1	Visceral adipose tissue	1.000000e-06
GCST007231_7	Tuberculosis	7.000000e-06
GCST007950_13	Type 2 diabetes and end-stage kidney disease in APOL1 risk genotype negative individuals	2.000000e-09
GCST009391_56	Metabolite levels	5.000000e-06
GCST011388_1	Vaginal microbiome composition (L. crispatus)	5.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004340	body mass index
EFO:0010474	cystathionine measurement
EFO:0011013	vaginal microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases abundance	4
Valproic Acid	decreases methylation, increases expression	4
bisphenol A	affects methylation, decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
o,p’-DDT	decreases expression	1
sulforaphane	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
ciglitazone	increases expression, affects binding	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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