HMGN1

Summary

HMGN1 (high mobility group nucleosome binding domain 1, HGNC:4984) is a protein-coding gene on chromosome 21q22.2, encoding Non-histone chromosomal protein HMG-14 (P05114). Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer.

The protein encoded by this gene binds nucleosomal DNA and is associated with transcriptionally active chromatin. Along with a similar protein, HMG17, the encoded protein may help maintain an open chromatin configuration around transcribable genes.

Source: NCBI Gene 3150 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 41 total — 1 pathogenic
• MANE Select transcript: NM_004965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4984
Approved symbol	HMGN1
Name	high mobility group nucleosome binding domain 1
Location	21q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ27265, FLJ31471, MGC104230, MGC117425
Ensembl gene	ENSG00000205581
Ensembl biotype	protein_coding
OMIM	163920
Entrez	3150

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 13 protein_coding, 7 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay, 5 retained_intron

ENST00000288344, ENST00000380747, ENST00000380748, ENST00000380749, ENST00000419378, ENST00000431390, ENST00000436324, ENST00000443046, ENST00000463631, ENST00000464078, ENST00000471260, ENST00000479586, ENST00000482192, ENST00000482733, ENST00000485550, ENST00000486741, ENST00000489072, ENST00000490032, ENST00000491183, ENST00000492280, ENST00000652622, ENST00000910672, ENST00000910673, ENST00000910674, ENST00000910675, ENST00000910676, ENST00000910677, ENST00000910678, ENST00000910679, ENST00000946299, ENST00000946300

RefSeq mRNA: 1 — MANE Select: NM_004965 NM_004965

CCDS: CCDS33559

Canonical transcript exons

ENST00000380749 — 6 exons

Exon	Start	End
ENSE00001599611	39348903	39349088
ENSE00003532954	39345146	39345274
ENSE00003552745	39348545	39348577
ENSE00003585321	39348422	39348451
ENSE00003605975	39348292	39348339
ENSE00003659677	39342315	39343159

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.0860 / max 1112.6090, expressed in 1823 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190500	47.0055	1820
190492	10.6837	1707
190499	9.5153	1713
190497	6.0008	1588
190493	2.7661	1229
190498	0.8539	536
190495	0.7628	424
190496	0.7522	396
190501	0.4079	182
190494	0.2863	128

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.56	gold quality
ganglionic eminence	UBERON:0004023	99.55	gold quality
embryo	UBERON:0000922	99.54	gold quality
endometrium	UBERON:0001295	99.28	gold quality
cortical plate	UBERON:0005343	99.14	gold quality
right uterine tube	UBERON:0001302	98.96	gold quality
vermiform appendix	UBERON:0001154	98.95	gold quality
lymph node	UBERON:0000029	98.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.84	gold quality
rectum	UBERON:0001052	98.77	gold quality
islet of Langerhans	UBERON:0000006	98.72	gold quality
bone element	UBERON:0001474	98.60	gold quality
bone marrow	UBERON:0002371	98.60	gold quality
tonsil	UBERON:0002372	98.56	gold quality
right testis	UBERON:0004534	98.55	gold quality
bone marrow cell	CL:0002092	98.53	gold quality
pancreas	UBERON:0001264	98.52	gold quality
thyroid gland	UBERON:0002046	98.49	gold quality
body of pancreas	UBERON:0001150	98.48	gold quality
duodenum	UBERON:0002114	98.48	gold quality
adenohypophysis	UBERON:0002196	98.44	gold quality
left lobe of thyroid gland	UBERON:0001120	98.43	gold quality
esophagus mucosa	UBERON:0002469	98.43	gold quality
prostate gland	UBERON:0002367	98.42	gold quality
left testis	UBERON:0004533	98.42	gold quality
lower esophagus mucosa	UBERON:0035834	98.41	gold quality
ovary	UBERON:0000992	98.38	gold quality
esophagus	UBERON:0001043	98.38	gold quality
right lobe of thyroid gland	UBERON:0001119	98.37	gold quality
pituitary gland	UBERON:0000007	98.36	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	4629.82
E-GEOD-139324	yes	2137.36
E-MTAB-8410	yes	2133.50
E-CURD-122	yes	1321.45
E-HCAD-4	yes	46.33
E-CURD-112	yes	40.77
E-GEOD-137537	yes	28.06
E-CURD-46	yes	25.44
E-GEOD-125970	yes	24.66
E-HCAD-1	yes	17.78
E-MTAB-10042	yes	17.52
E-MTAB-8142	yes	9.91
E-MTAB-10553	yes	8.72
E-CURD-88	yes	5.77
E-MTAB-10596	no	1254.40

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
FOS	Unknown
PCNA	Unknown
TFF1	Unknown

Upstream regulators (CollecTRI, top): E2F1, ESR1, REL, ZNF219

miRNA regulators (miRDB)

86 targeting HMGN1, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7C-3P	99.95	73.42	2862

Literature-anchored findings (GeneRIF, showing 19)

• Results show that four serine residues, i.e., Ser6, Ser85, Ser88, and Ser98, can be phosphorylated in high mobility group N1 (HMGN1). (PMID:15147216)
• HMGN1 optimizes the cellular response to ionizing radiation and to other tumorigenic events; therefore, loss of this protein increases the tumor burden in mice. (PMID:16061652)
• SWI/SNF functions independently of HMGN1 (PMID:16253989)
• Five serine residues, i.e., Ser6, Ser7, Ser85, Ser88, and Ser98, in HMGN1 can be phosphorylated by the kinase in vitro, and Ser6, Ser7, and Ser85 were new sites among these five sites. (PMID:16729963)
• These findings indicate that HMGN1 regulates the expression of particular genes via specific protein-protein interactions with transcription factors at target gene regulatory regions. (PMID:17938209)
• These studies demonstrate that the mode of binding of HMGNs to chromatin is cell cycle dependent. (PMID:18287527)
• HMGN1 (HMG14) and HMGN2 (HMG17) potently repress ATP-dependent chromatin remodeling by four different molecular motor proteins. (PMID:19524541)
• HMGN1 is not randomly distributed throughout the genome. Instead, the protein preferentially localizes to DNase I hypersensitive (HS) sites, promoters, functional enhancers, and transcription factor binding sites. (PMID:21173166)
• HMGN1 regulates the expression of methyl CpG-binding protein 2 (MECP2) in mouse and human, and affects the behavior of mice (PMID:22009741)
• extracellular HMGN1 acts as a novel alarmin critical for LPS-induced development of innate and adaptive immune responses. (PMID:22184635)
• nucleosome binding protein HMGN1 as a new PCNA-interacting protein that enhances the binding of PCNA to chromatin (PMID:22393258)
• HMGN1 can serve as a useful clinical parameter for evaluating disease progression and predicting the outcomes for early-stage patients with non-small cell lung cancer . (PMID:26113410)
• RNA-seq evidence of biallelic expression of HMGN1 and 10 neighboring genes in at least one primary human tissue tested indicates that the expression of HMGN1 is uncoupled from the control of the maternally inherited 5mCpG imprints at the WRB differentially methylated region (DMR) in disomic controls or trisomy (Down syndrome) individuals. (PMID:27100087)
• HMGN1 and HMGN 2 remodel core and linker histone tail domains within chromatin. (PMID:28973435)
• Studies indicate that high mobility group nucleosome binding domain 1 (HMGN1) preferentially promotes Th1-type immunity, which makes it relevant for the fields of vaccinology, autoimmunity, and oncoimmunology [Review]. (PMID:29503123)
• Transcriptional amplification downstream of HMGN1 is enriched for stage-specific programs of B cells and B cell acute lymphoblastic leukemia, dependent on the developmental cellular context. (PMID:30428356)
• HMGN1 plays a significant role in CRLF2 driven Down Syndrome leukemia and provides a potential therapeutic target in this high-risk cohort. (PMID:34857887)
• Spatial and Temporal Expression of High-Mobility-Group Nucleosome-Binding (HMGN) Genes in Brain Areas Associated with Cognition in Individuals with Down Syndrome. (PMID:34946949)
• Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain. (PMID:36463299)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmgn6	ENSDARG00000087636
mus_musculus	Hmgn1	ENSMUSG00000040681
rattus_norvegicus	Hmgn1l1	ENSRNOG00000047566
rattus_norvegicus	Hmgn1	ENSRNOG00000048226

Paralogs (3): HMGN3 (ENSG00000118418), HMGN4 (ENSG00000182952), HMGN2 (ENSG00000198830)

Protein

Protein identifiers

Non-histone chromosomal protein HMG-14 — P05114 (reviewed: P05114)

Alternative names: High mobility group nucleosome-binding domain-containing protein 1

All UniProt accessions (7): A0A494C035, A6NEL0, A6NL93, F2Z2W6, F2Z2Y5, P05114, H7BXJ5

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation. Inhibits the phosphorylation of nucleosomal histones H3 and H2A by RPS6KA5/MSK1 and RPS6KA3/RSK2.

Subunit / interactions. Interacts with transcriptional regulator SEHBP.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Phosphorylation on Ser-21 and Ser-25 weakens binding to nucleosomes and increases the rate of H3 phosphorylation. Phosphorylation favors cytoplasmic localization.

Similarity. Belongs to the HMGN family.

RefSeq proteins (1): NP_004956* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000079	HMGN_fam	Family

Pfam: PF01101

UniProt features (17 total): modified residue 12, compositionally biased region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05114-F1	63.35	0.00

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 (12): 27, 81, 82, 86, 89, 99, 7, 8, 14, 21, 25, 25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 214 (showing top): GOBP_RESPONSE_TO_UV_C, GCM_MSN, GOBP_TRANSCRIPTION_COUPLED_NUCLEOTIDE_EXCISION_REPAIR, MORF_UBE2I, MORF_HDAC1, MORF_RAD21, TACAATC_MIR508, PUJANA_CHEK2_PCC_NETWORK, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, CTCTAGA_MIR526C_MIR518F_MIR526A, GOBP_NUCLEOTIDE_EXCISION_REPAIR, MORF_SKP1A, GCM_PSME1, GCM_PPP1CC, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (11): pyrimidine dimer repair by nucleotide-excision repair (GO:0000720), transcription-coupled nucleotide-excision repair (GO:0006283), chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), response to UV-B (GO:0010224), response to UV-C (GO:0010225), positive regulation of DNA-templated transcription, elongation (GO:0032786), regulation of development, heterochronic (GO:0040034), post-embryonic camera-type eye morphogenesis (GO:0048597), regulation of epithelial cell proliferation (GO:0050678), RNA processing (GO:0006396)

GO Molecular Function (4): DNA binding (GO:0003677), chromatin binding (GO:0003682), nucleosomal DNA binding (GO:0031492), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), female germ cell nucleus (GO:0001674), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleotide-excision repair	2
response to UV	2
binding	2
nuclear lumen	2
pyrimidine dimer repair	1
cellular component organization	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription elongation	1
regulation of DNA-templated transcription elongation	1
positive regulation of DNA-templated transcription	1
regulation of developmental process	1
post-embryonic camera-type eye development	1
post-embryonic eye morphogenesis	1
camera-type eye morphogenesis	1
regulation of cell population proliferation	1
epithelial cell proliferation	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
chromatin DNA binding	1
nucleosome binding	1
chromosome	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMGN1	HMGN2	P05204	986
HMGN1	HMGN5	P82970	956
HMGN1	XAB2	Q9HCS7	936
HMGN1	ZNF219	Q9P2Y4	907
HMGN1	SH3BGR	P55822	875
HMGN1	TCEA1	P23193	874
HMGN1	SH3BGRL	O75368	834
HMGN1	GET1	O00258	802
HMGN1	UVSSA	Q2YD98	790
HMGN1	ERCC8	Q13216	764
HMGN1	ERCC6	Q03468	753
HMGN1	DDB1	Q16531	727
HMGN1	CUL4A	Q13619	695
HMGN1	H1-0	P07305	693
HMGN1	EP300	Q09472	655

IntAct

63 interactions, top by confidence:

A	B	Type	Score
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
BRAF	NRAS	psi-mi:“MI:0914”(association)	0.860
STBD1	GABARAP	psi-mi:“MI:0914”(association)	0.760
	HMGN1	psi-mi:“MI:0407”(direct interaction)	0.440
MAGEA4	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
LCP2	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
RAB11FIP5	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
SUGP2	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
CACNG2	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
ANK3	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
PLAGL2	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
DCDC2B	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
H2BC12L	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
H2BC9	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
ZNF653	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
H2AC12	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
H2AC4	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
HMGN1	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
TERF2	HMGN1	psi-mi:“MI:0915”(physical association)	0.370
GSK3A	HMGN1	psi-mi:“MI:0915”(physical association)	0.370
HMGN1	NFE2	psi-mi:“MI:0915”(physical association)	0.370
SLC38A3	HMGN1	psi-mi:“MI:0915”(physical association)	0.370
CHEK2	HMGN1	psi-mi:“MI:0915”(physical association)	0.370
MYH6	BDP1	psi-mi:“MI:0914”(association)	0.350
PDK1	VWA8	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
ARHGAP35	CSTB	psi-mi:“MI:0914”(association)	0.350
ARHGEF19	NUP42	psi-mi:“MI:0914”(association)	0.350
ATRIP	HMGN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (221): HMGN1 (Affinity Capture-MS), HMGN1 (Two-hybrid), HMGN1 (Proximity Label-MS), HMGN1 (Proximity Label-MS), HMGN1 (Affinity Capture-MS), HMGN1 (Affinity Capture-MS), HMGN1 (Biochemical Activity), HMGN1 (Biochemical Activity), HMGN1 (Reconstituted Complex), HMGN1 (Affinity Capture-MS), HMGN1 (Affinity Capture-MS), HMGN1 (Affinity Capture-MS), HMGN1 (Affinity Capture-MS), HMGN1 (Affinity Capture-MS), HMGN1 (Affinity Capture-RNA)

ESM2 similar proteins: A2QUR1, A2WMG6, B0WQG0, O42932, O77788, P05114, P06180, P06302, P12036, P12274, P12902, P15308, P16527, P23614, P26645, P27864, P29746, P29966, P30009, P34618, P50887, P54938, P80723, P80724, P91027, Q02508, Q05175, Q0JPA6, Q10020, Q17Q32, Q1RM09, Q23794, Q3ZBV4, Q54LY8, Q56WH4, Q56WK6, Q56ZI2, Q5R715, Q5ZIR5, Q6PD99

Diamond homologs: P02316, P05114, P12274, P12902, P18608, Q15651, Q5R715, Q66H40, Q9DCB1, O00479, P02314, P05204, P82970, Q3ZBV4, P02313, P09602, P18437, P80272, Q5RAA0, Q5ZIR5, Q711A6

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
RPS6KA3	“down-regulates activity”	HMGN1	phosphorylation
PRKACA	“down-regulates activity”	HMGN1	phosphorylation
CSNK2A1	down-regulates	HMGN1	phosphorylation
PRKCA	down-regulates	HMGN1	phosphorylation
RPS6KA3	unknown	HMGN1	phosphorylation
RPS6KA4	unknown	HMGN1	phosphorylation
RPS6KA5	“down-regulates activity”	HMGN1	phosphorylation
HMGN1	down-regulates	Chromatine_condensation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Packaging Of Telomere Ends	5	20.7×	1e-03
Recognition and association of DNA glycosylase with site containing an affected purine	5	19.2×	1e-03
Cleavage of the damaged purine	5	19.2×	1e-03
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	5	17.4×	1e-03
Cleavage of the damaged pyrimidine	5	17.4×	1e-03
Inhibition of DNA recombination at telomere	5	15.8×	2e-03
DNA Damage/Telomere Stress Induced Senescence	5	15.4×	2e-03
Meiotic synapsis	5	13.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
443778	GRCh37/hg19 21q22.13-22.3(chr21:37914123-48097372)x1	Pathogenic

SpliceAI

1285 predictions. Top by Δscore:

Variant	Effect	Δscore
21:39343158:CT:C	acceptor_gain	1.0000
21:39345142:TGA:T	donor_loss	1.0000
21:39345144:A:AG	donor_loss	1.0000
21:39345144:ACCT:A	donor_gain	1.0000
21:39345145:CCTC:C	donor_gain	1.0000
21:39345147:T:TA	donor_gain	1.0000
21:39345270:TTATC:T	acceptor_gain	1.0000
21:39345273:TCCT:T	acceptor_loss	1.0000
21:39345274:CCT:C	acceptor_loss	1.0000
21:39347959:T:TC	acceptor_gain	1.0000
21:39348286:GCTTA:G	donor_loss	1.0000
21:39348287:CTTAC:C	donor_loss	1.0000
21:39348288:TTAC:T	donor_loss	1.0000
21:39348289:TACCT:T	donor_loss	1.0000
21:39348290:A:AC	donor_gain	1.0000
21:39348290:ACCT:A	donor_loss	1.0000
21:39348291:C:CC	donor_gain	1.0000
21:39348420:A:AC	donor_gain	1.0000
21:39348421:C:CC	donor_gain	1.0000
21:39348452:C:CC	acceptor_gain	1.0000
21:39348453:T:C	acceptor_gain	1.0000
21:39348453:T:TC	acceptor_gain	1.0000
21:39348541:TCA:T	donor_loss	1.0000
21:39348543:A:AC	donor_gain	1.0000
21:39348544:C:CC	donor_gain	1.0000
21:39348544:CCT:C	donor_gain	1.0000
21:39343160:C:CC	acceptor_gain	0.9900
21:39345140:TCTGA:T	donor_loss	0.9900
21:39345141:CTGAC:C	donor_loss	0.9900
21:39345148:C:A	donor_gain	0.9900

AlphaMissense

643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:39348429:A:G	L24S	0.990
21:39348440:T:A	R20S	0.987
21:39348440:T:G	R20S	0.987
21:39348443:C:A	R19S	0.983
21:39348443:C:G	R19S	0.983
21:39348444:C:A	R19M	0.980
21:39348907:C:A	R4M	0.978
21:39348908:T:A	R4W	0.975
21:39348913:G:T	P2H	0.972
21:39348429:A:C	L24W	0.970
21:39348906:C:A	R4S	0.966
21:39348906:C:G	R4S	0.966
21:39348445:T:A	R19W	0.965
21:39348909:C:A	K3N	0.964
21:39348909:C:G	K3N	0.964
21:39348913:G:A	P2L	0.963
21:39348441:C:G	R20T	0.962
21:39348444:C:G	R19T	0.958
21:39348441:C:A	R20I	0.948
21:39348907:C:G	R4T	0.941
21:39348914:G:A	P2S	0.936
21:39348910:T:A	K3M	0.930
21:39348914:G:T	P2T	0.922
21:39348442:T:C	R20G	0.921
21:39348433:G:A	R23W	0.909
21:39348446:C:A	K18N	0.909
21:39348446:C:G	K18N	0.909
21:39348450:G:T	P17H	0.908
21:39348903:C:A	K5N	0.905
21:39348903:C:G	K5N	0.905

dbSNP variants (sampled 300 via entrez): RS1000433303 (21:39348761 G>A,T), RS1000697562 (21:39343010 G>C), RS1000868318 (21:39347932 G>A), RS1001153863 (21:39342273 T>A), RS1001207425 (21:39348072 C>G,T), RS1001308315 (21:39347329 G>A), RS1002209777 (21:39343264 A>G), RS1002614922 (21:39348979 G>A,C), RS1002945277 (21:39346011 A>G), RS1003156867 (21:39344663 C>A,G), RS1003770538 (21:39346805 C>T), RS1003895646 (21:39350625 G>A,T), RS1004226944 (21:39342423 C>A,T), RS1004277763 (21:39341855 T>C), RS1004509138 (21:39342724 T>C)

Disease associations

OMIM: gene MIM:163920 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007327_37	Smoking status (ever vs never smokers)	8.000000e-09
GCST010245_69	LDL cholesterol levels	9.000000e-11
GCST012232_39	Lipoprotein (a) levels	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0006925	lipoprotein A measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, increases expression, affects cotreatment, affects expression, increases abundance	2
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Ozone	increases abundance, affects cotreatment, increases oxidation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
ochratoxin A	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
chloropicrin	affects expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Citrinin	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2T5	SEES3-1V human HMGN1, clone1	Embryonic stem cell	Male
CVCL_A2T6	SEES3-1V human HMGN1, clone2	Embryonic stem cell	Male
CVCL_A2T7	SEES3-1V human HMGN1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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