H2AC17

Summary

H2AC17 (H2A clustered histone 17, HGNC:4735) is a protein-coding gene on chromosome 6p22.1, encoding Histone H2A type 1 (P0C0S8). Core component of nucleosome. It is a selective cancer dependency (DepMap: 79.5% of cell lines).

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3.

Source: NCBI Gene 8336 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 27 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 79.5% of screened cell lines
• MANE Select transcript: NM_003514

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4735
Approved symbol	H2AC17
Name	H2A clustered histone 17
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	H2A/n, H2A.1
Ensembl gene	ENSG00000278677
Ensembl biotype	protein_coding
OMIM	602796
Entrez	8336

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000359611

RefSeq mRNA: 1 — MANE Select: NM_003514 NM_003514

CCDS: CCDS4639

Canonical transcript exons

ENST00000359611 — 1 exons

Exon	Start	End
ENSE00001660121	27892699	27893185

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1617.0280 / max 53191.5572, expressed in 1761 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72393	1614.4676	1761
72392	2.5604	488

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	98.69	gold quality
adrenal tissue	UBERON:0018303	92.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.77	gold quality
bone marrow	UBERON:0002371	84.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.20	gold quality
calcaneal tendon	UBERON:0003701	78.55	gold quality
monocyte	CL:0000576	77.80	gold quality
leukocyte	CL:0000738	75.97	gold quality
corpus callosum	UBERON:0002336	72.51	gold quality
tonsil	UBERON:0002372	70.10	gold quality
mucosa of transverse colon	UBERON:0004991	68.92	gold quality
blood	UBERON:0000178	68.18	gold quality
granulocyte	CL:0000094	68.17	gold quality
lower esophagus mucosa	UBERON:0035834	65.80	gold quality
colonic epithelium	UBERON:0000397	63.01	gold quality
esophagus mucosa	UBERON:0002469	57.72	gold quality
placenta	UBERON:0001987	57.43	gold quality
lymph node	UBERON:0000029	57.12	gold quality
ganglionic eminence	UBERON:0004023	54.82	gold quality
thyroid gland	UBERON:0002046	54.20	gold quality
ventricular zone	UBERON:0003053	54.12	gold quality
right lobe of thyroid gland	UBERON:0001119	53.89	gold quality
left lobe of thyroid gland	UBERON:0001120	53.76	gold quality
spleen	UBERON:0002106	53.70	gold quality
rectum	UBERON:0001052	53.34	gold quality
right adrenal gland	UBERON:0001233	52.77	gold quality
adrenal gland	UBERON:0002369	52.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	52.64	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	51.99	gold quality
lung	UBERON:0002048	51.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-79	yes	1232.20
E-MTAB-6911	yes	379.43
E-MTAB-9467	yes	30.77
E-CURD-122	yes	24.71
E-ANND-3	yes	5.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 79.5% of screened cell lines.

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	His2A:CG31618	FBGN0051618
drosophila_melanogaster	His2A:CG33808	FBGN0053808
drosophila_melanogaster	His2A:CG33814	FBGN0053814
drosophila_melanogaster	His2A:CG33817	FBGN0053817
drosophila_melanogaster	His2A:CG33820	FBGN0053820
drosophila_melanogaster	His2A:CG33823	FBGN0053823
drosophila_melanogaster	His2A:CG33826	FBGN0053826
drosophila_melanogaster	His2A:CG33829	FBGN0053829
drosophila_melanogaster	His2A:CG33832	FBGN0053832
drosophila_melanogaster	His2A:CG33835	FBGN0053835
drosophila_melanogaster	His2A:CG33838	FBGN0053838
drosophila_melanogaster	His2A:CG33841	FBGN0053841
drosophila_melanogaster	His2A:CG33844	FBGN0053844
drosophila_melanogaster	His2A:CG33847	FBGN0053847
drosophila_melanogaster	His2A:CG33850	FBGN0053850
drosophila_melanogaster	His2A:CG33853	FBGN0053853
drosophila_melanogaster	His2A:CG33856	FBGN0053856
drosophila_melanogaster	His2A:CG33859	FBGN0053859
drosophila_melanogaster	His2A:CG33862	FBGN0053862
drosophila_melanogaster	His2A:CG33865	FBGN0053865

Paralogs (27): MACROH2A2 (ENSG00000099284), H2AZ2 (ENSG00000105968), MACROH2A1 (ENSG00000113648), H2AZ1 (ENSG00000164032), H2AC1 (ENSG00000164508), H2AC6 (ENSG00000180573), H2AC25 (ENSG00000181218), H2AC20 (ENSG00000184260), H2AC21 (ENSG00000184270), H2AX (ENSG00000188486), H2AC13 (ENSG00000196747), H2AC11 (ENSG00000196787), H2AC7 (ENSG00000196866), H2AL3 (ENSG00000229674), H2AJ (ENSG00000246705), H2AL1Q (ENSG00000249467), H2AB1 (ENSG00000274183), H2AC12 (ENSG00000274997), H2AC15 (ENSG00000275221), H2AC14 (ENSG00000276368), H2AC16 (ENSG00000276903), H2AC8 (ENSG00000277075), H2AB3 (ENSG00000277745), H2AB2 (ENSG00000277858), H2AC4 (ENSG00000278463), H2AC18 (ENSG00000288825), H2AC19 (ENSG00000288859)

Protein

Protein identifiers

Histone H2A type 1 — P0C0S8 (reviewed: P0C0S8)

Alternative names: Histone H2A/ptl

All UniProt accessions (2): P0C0S8, A4FTV9

UniProt curated annotations — full annotation on UniProt →

Function. Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

Subunit / interactions. The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with VRK1; the interaction is mediated by the nucleosome acidic patch, a cluster of negatively charged residues of H2A and H2B forming a cleft within the nucleosome core.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Deiminated on Arg-4 in granulocytes upon calcium entry. Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of ‘Lys-27’ of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers. Following DNA double-strand breaks (DSBs), it is ubiquitinated through ‘Lys-63’ linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and ‘Lys-63’-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend ‘Lys-63’-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired. H2AK119Ub and ionizing radiation-induced ‘Lys-63’-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events. Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription. Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage. Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex. Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes. Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.

Similarity. Belongs to the histone H2A family.

RefSeq proteins (1): NP_003505* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002119	Histone_H2A	Family
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR032454	Histone_H2A_C	Domain
IPR032458	Histone_H2A_CS	Conserved_site

Pfam: PF00125, PF16211

UniProt features (63 total): modified residue 36, mutagenesis site 9, helix 6, strand 4, cross-link 3, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

65 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4QYL	X-RAY DIFFRACTION	1.8
10YE	ELECTRON MICROSCOPY	2.5
8GUK	ELECTRON MICROSCOPY	2.51
9Y46	ELECTRON MICROSCOPY	2.59
10XZ	ELECTRON MICROSCOPY	2.6
10YA	ELECTRON MICROSCOPY	2.7
10YC	ELECTRON MICROSCOPY	2.7
9Y47	ELECTRON MICROSCOPY	2.74
10YB	ELECTRON MICROSCOPY	2.8
10YD	ELECTRON MICROSCOPY	2.8
7E8D	ELECTRON MICROSCOPY	2.8
8GUJ	ELECTRON MICROSCOPY	2.8
8GUI	ELECTRON MICROSCOPY	2.81
9SI3	ELECTRON MICROSCOPY	2.83
9SJ5	ELECTRON MICROSCOPY	2.85
9SI9	ELECTRON MICROSCOPY	2.86
6X59	ELECTRON MICROSCOPY	2.98
7TAN	ELECTRON MICROSCOPY	3
8VWU	ELECTRON MICROSCOPY	3
9BE6	ELECTRON MICROSCOPY	3
7U51	ELECTRON MICROSCOPY	3.1
8QZM	ELECTRON MICROSCOPY	3.1
8VOB	ELECTRON MICROSCOPY	3.1
8VWS	ELECTRON MICROSCOPY	3.1
9DWF	ELECTRON MICROSCOPY	3.1
9E2Q	ELECTRON MICROSCOPY	3.14
9NQU	ELECTRON MICROSCOPY	3.16
7UV9	ELECTRON MICROSCOPY	3.2
9E0R	ELECTRON MICROSCOPY	3.2
7JO9	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C0S8-F1	91.34	0.80

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 (39): 10, 10, 10, 10, 14, 14, 16, 37, 37, 37, 37, 75, 76, 96, 96, 96, 96, 96, 100, 105 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
2	blocks the inhibition of transcription by rps6ka5/msk1.
57	no effect on interaction with vrk1.
62	decreased interaction with vrk1.
65	decreased interaction with vrk1.
73	no effect on interaction with vrk1.
90	no effect on interaction with vrk1.
91	decreased interaction with vrk1.
92	no effect on interaction with vrk1.
93	decreased interaction with vrk1.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-3214847	HATs acetylate histones
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-5689603	UCH proteinases
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5689901	Metalloprotease DUBs
R-HSA-9609690	HCMV Early Events
R-HSA-9610379	HCMV Late Events
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 128 (showing top): FISCHER_G1_S_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, FISCHER_DREAM_TARGETS, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, DANG_BOUND_BY_MYC, TTTNNANAGCYR_UNKNOWN, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOCC_PROTEIN_DNA_COMPLEX, BENPORATH_MYC_MAX_TARGETS, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, HEIDENBLAD_AMPLICON_8Q24_UP

GO Biological Process (1): heterochromatin formation (GO:0031507)

GO Molecular Function (5): DNA binding (GO:0003677), enzyme binding (GO:0019899), structural constituent of chromatin (GO:0030527), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (4): nucleosome (GO:0000786), nucleus (GO:0005634), extracellular exosome (GO:0070062), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Chromatin modifying enzymes	3
Deubiquitination	3
HCMV Infection	2
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
nucleic acid binding	1
protein binding	1
structural molecule activity	1
protein dimerization activity	1
binding	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

205 interactions, top by confidence:

A	B	Type	Score
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
OPG044	DDX3X	psi-mi:“MI:0914”(association)	0.730
TP53BP1	H2AC11	psi-mi:“MI:0915”(physical association)	0.670
H2AC11	UBB	psi-mi:“MI:0915”(physical association)	0.650
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640

BioGRID (762): APPBP2 (Two-hybrid), NOTCH2NL (Two-hybrid), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS)

ESM2 similar proteins: A1A4R1, A9UMV8, C0HKE1, C0HKE2, C0HKE3, C0HKE4, C0HKE5, C0HKE6, C0HKE7, C0HKE8, C0HKE9, P02262, P02263, P02270, P04908, P06897, P0C0S8, P0C0S9, P0C169, P0C170, P0CC09, P13912, P19178, P20671, P21896, P27325, P35061, P35062, P70082, P84052, Q07135, Q16777, Q3ZBX9, Q4FZT6, Q4R3X5, Q64522, Q64523, Q64598, Q6FI13, Q6GSS7

Diamond homologs: A0A097I1R9, A0A097I2B5, A0A0D2UG83, A1A4R1, A1CJ10, A1D8G8, A3LXE7, A3LZZ0, A5DBG4, A5DJJ2, A5DWF1, A5DXC6, A9UMV8, C0HKE1, C0HKE2, C0HKE3, C0HKE4, C0HKE5, C0HKE6, C0HKE7, C0HKE8, C0HKE9, L7HZV6, O74268, P02262, P02263, P02264, P04908, P04909, P04910, P04911, P04912, P06897, P07793, P08844, P0C0S8, P0C0S9, P0C169, P0C170, P0C952

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
RPS6KA5	up-regulates	H2AC11	phosphorylation
RNF8	up-regulates	H2AC11	ubiquitination
BRCC3	down-regulates	H2AC11	deubiquitination
H2AC11	up-regulates	RNF168	binding
BUB1	unknown	H2AC11	phosphorylation
H2AC11	“up-regulates activity”	SGO1	relocalization
SLBP	“up-regulates quantity by expression”	H2AC11	“translation regulation”
DZIP3	“up-regulates activity”	H2AC11	monoubiquitination
TRPM6	“down-regulates activity”	H2AC11	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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
Transport of Mature Transcript to Cytoplasm	5	16.1×	2e-04
Replacement of protamines by nucleosomes in the male pronucleus	6	13.8×	9e-05
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	13	13.0×	1e-08
Peptide chain elongation	12	12.9×	2e-08
Viral mRNA Translation	12	12.9×	2e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	12	12.8×	2e-08
Transcriptional Regulation by E2F6	5	12.4×	6e-04
Selenocysteine synthesis	12	12.2×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	14	15.2×	4e-10
base-excision repair	5	13.8×	5e-03
heterochromatin formation	7	10.5×	1e-03
negative regulation of translation	7	8.1×	5e-03
nucleosome assembly	9	7.4×	1e-03
translation	12	7.2×	5e-05

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
800317	NM_003514.2(H2AC17):c.364G>A (p.Glu122Lys)	Likely pathogenic

SpliceAI

37 predictions. Top by Δscore:

Variant	Effect	Δscore
6:27892770:G:C	donor_gain	0.7300
6:27892763:G:A	donor_gain	0.6300
6:27892849:CT:C	donor_gain	0.5800
6:27892850:TT:T	donor_gain	0.5800
6:27892851:TT:T	donor_gain	0.5800
6:27892980:TCCAG:T	donor_gain	0.4600
6:27892981:CCAGC:C	donor_gain	0.4600
6:27892759:A:AC	donor_gain	0.4400
6:27892760:C:CC	donor_gain	0.4400
6:27892763:GC:G	donor_gain	0.3600
6:27892764:CC:C	donor_gain	0.3600
6:27892761:T:C	donor_gain	0.3500
6:27892855:C:CT	donor_gain	0.3100
6:27892856:A:T	donor_gain	0.2800
6:27893141:T:TA	donor_gain	0.2800
6:27892759:ACTTG:A	donor_gain	0.2700
6:27892760:CTTGC:C	donor_gain	0.2700
6:27893127:C:CA	donor_gain	0.2700
6:27893135:G:A	donor_gain	0.2700
6:27892763:GCCCT:G	donor_gain	0.2600
6:27892760:CTTG:C	donor_gain	0.2500
6:27892764:CCCTT:C	donor_gain	0.2500
6:27892765:CC:C	donor_gain	0.2500
6:27892766:C:T	donor_gain	0.2500
6:27893063:T:TA	donor_gain	0.2500
6:27892762:TGCCC:T	donor_gain	0.2400
6:27892892:CAG:C	acceptor_gain	0.2300
6:27892769:AG:A	donor_gain	0.2200
6:27892853:A:AC	donor_gain	0.2200
6:27892854:C:CC	donor_gain	0.2200

AlphaMissense

819 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:27892831:C:G	G107R	1.000
6:27892834:C:G	G106R	1.000
6:27892878:T:A	D91V	1.000
6:27892878:T:C	D91G	1.000
6:27892878:T:G	D91A	1.000
6:27892879:C:G	D91H	1.000
6:27892884:C:G	R89P	1.000
6:27892893:A:G	L86P	1.000
6:27892938:G:T	A71D	1.000
6:27892947:C:A	G68V	1.000
6:27892947:C:T	G68D	1.000
6:27892948:C:G	G68R	1.000
6:27892953:A:G	L66P	1.000
6:27892959:A:G	L64P	1.000
6:27892974:A:G	L59P	1.000
6:27892978:A:G	Y58H	1.000
6:27892815:A:G	I112T	0.999
6:27892815:A:T	I112N	0.999
6:27892821:G:T	P110H	0.999
6:27892830:C:A	G107V	0.999
6:27892830:C:T	G107D	0.999
6:27892831:C:A	G107C	0.999
6:27892831:C:T	G107S	0.999
6:27892833:C:A	G106V	0.999
6:27892833:C:T	G106D	0.999
6:27892834:C:A	G106C	0.999
6:27892842:A:T	I103N	0.999
6:27892869:A:G	L94P	0.999
6:27892869:A:T	L94H	0.999
6:27892877:G:C	D91E	0.999

dbSNP variants (sampled 300 via entrez): RS1000538626 (6:27892660 G>A,C), RS1000653439 (6:27892473 AC>A), RS1001825482 (6:27893057 C>A,G,T), RS1002546427 (6:27895179 A>G), RS1003073035 (6:27894780 C>T), RS1003892930 (6:27894202 G>A,C), RS1007560035 (6:27892495 T>C), RS1008011219 (6:27893207 G>A,T), RS1008089069 (6:27892245 G>T), RS1009911597 (6:27893098 G>C,T), RS1010462329 (6:27892423 CT>C), RS1011592663 (6:27894288 G>A), RS1012480526 (6:27894695 A>G), RS1014680341 (6:27893022 C>A,G,T), RS1014844489 (6:27892733 G>A)

Disease associations

OMIM: gene MIM:602796 | disease phenotypes: MIM:254500

GenCC curated gene-disease

Mondo (1): plasma cell myeloma (MONDO:0009693)

Orphanet (2): Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_115	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_116	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_166	Autism spectrum disorder or schizophrenia	4.000000e-24
GCST004521_22	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004521_23	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004521_6	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_73	Autism spectrum disorder or schizophrenia	8.000000e-11
GCST008921_6	Asthma and major depressive disorder	1.000000e-09
GCST010002_50	Refractive error	4.000000e-34
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	3
(+)-JQ1 compound	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Formaldehyde	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
afuresertib	decreases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
versicolorin A	decreases expression	1
cupric oxide	increases expression	1
chromium hexavalent ion	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
MT19c compound	decreases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Berberine	decreases expression	1
Cannabidiol	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Doxorubicin	affects expression	1
Ethyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	PHASE4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	PHASE4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	PHASE4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting