HSPB2

Summary

HSPB2 (heat shock protein family B (small) member 2, HGNC:5247) is a protein-coding gene on chromosome 11q23.1, encoding Heat shock protein beta-2 (Q16082). May regulate the kinase DMPK.

The protein encoded by this gene belongs to the superfamily of small heat-shock proteins containing a conservative alpha-crystallin domain at the C-terminal part of the molecule. The protein is expressed preferentially in the heart and skeletal muscle. This protein regulates Myotonic Dystrophy Protein Kinase, which plays an important role in maintenance of muscle structure and function.

Source: NCBI Gene 3316 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 4 total — 2 pathogenic
• MANE Select transcript: NM_001541

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5247
Approved symbol	HSPB2
Name	heat shock protein family B (small) member 2
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Aliases	Hs.78846, MKBP
Ensembl gene	ENSG00000170276
Ensembl biotype	protein_coding
OMIM	602179
Entrez	3316

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000304298, ENST00000941391

RefSeq mRNA: 1 — MANE Select: NM_001541 NM_001541

CCDS: CCDS8352

Canonical transcript exons

ENST00000304298 — 2 exons

Exon	Start	End
ENSE00001130746	111913441	111914093
ENSE00001130748	111912734	111912923

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.37.

FANTOM5 (CAGE): breadth broad, TPM avg 8.7846 / max 873.2447, expressed in 672 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116648	8.4516	733
116656	5.6064	588
116652	0.8530	185
116649	0.7983	312
116650	0.6357	280
116653	0.4300	74
116647	0.1719	70
116651	0.1383	51
116655	0.0838	20
116654	0.0672	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	98.37	gold quality
apex of heart	UBERON:0002098	98.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.83	gold quality
heart left ventricle	UBERON:0002084	97.65	gold quality
heart	UBERON:0000948	97.27	gold quality
gastrocnemius	UBERON:0001388	97.16	gold quality
muscle of leg	UBERON:0001383	96.71	gold quality
muscle organ	UBERON:0001630	96.62	gold quality
descending thoracic aorta	UBERON:0002345	96.44	gold quality
ascending aorta	UBERON:0001496	96.40	gold quality
thoracic aorta	UBERON:0001515	96.36	gold quality
popliteal artery	UBERON:0002250	96.20	gold quality
tibial artery	UBERON:0007610	96.19	gold quality
mucosa of stomach	UBERON:0001199	95.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.55	gold quality
left coronary artery	UBERON:0001626	95.40	gold quality
right coronary artery	UBERON:0001625	95.27	gold quality
adipose tissue	UBERON:0001013	95.07	gold quality
tibial nerve	UBERON:0001323	94.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.70	gold quality
omental fat pad	UBERON:0010414	94.60	gold quality
skeletal muscle tissue	UBERON:0001134	94.27	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.43	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.10	gold quality
lower esophagus	UBERON:0013473	93.01	gold quality
left uterine tube	UBERON:0001303	92.37	gold quality
metanephros cortex	UBERON:0010533	92.14	gold quality
body of uterus	UBERON:0009853	92.00	gold quality
endocervix	UBERON:0000458	91.96	gold quality
myometrium	UBERON:0001296	91.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, HSF1, NR3C1, SOX17, SP1, TP53

miRNA regulators (miRDB)

21 targeting HSPB2, 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-4500	99.99	72.72	2367
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4800-5P	97.22	65.91	324
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-3619-3P	95.59	65.99	428

Literature-anchored findings (GeneRIF, showing 40)

• HSP27 and alphaB-crystallin are increased, phosphorylated and localized in aggresomes when proteasome activity is inhibited (PMID:11926998)
• HSP27 nuclear staining can serve as a sensitive marker for skin irritation or cellular stress in excised skin (PMID:12473058)
• HSP72 biosynthesis was analyzed by an image processing, computer-assisted imaging method in an endothelial vascular cell line and compared to a hand-calculated method. No differences were seen. (PMID:12503731)
• Hsp27 regulates apoptosis through an ability to interact with key components of the apoptotic signalling pathway [review] (PMID:12510153)
• hsp72 reduces caspase-3-mediated proteolysis of FAK, an anti-apoptotic protein (PMID:12611892)
• Hsp27 plays a significant role in the IFN-gamma-induced sensitization of oral SCC cells to anticancer drugs (PMID:12700631)
• Data show that heat shock protein 72 suppressed extracellular signal-regulated kinase activation by protecting dual-specificity phosphatases and suppressing MEK1/2. (PMID:12748284)
• Associates with the I kappa B kinase complex regulates tumor necrosis factor alpha-induced NF-kappa B activation. (PMID:12829720)
• down regulation in neuronal and non-neuronal cells expressing mutant ataxin-3 (PMID:12832059)
• HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation (PMID:12897149)
• Phosphorylated HSP27 favors reduced bead motions that are probably due to stabilization of the actin cytoskeleton. (PMID:14729728)
• HSP27 may provide a neuroprotective effect in AD and other tauopathies (PMID:14963027)
• KNG modulate bone marrow derived stromal/preosteoblast cell proliferation and suppress etoposide-induced apoptosis through ERK and HSP27 activation, respectively. (PMID:16598774)
• Both heat and BPDE can induce the expressions of Hsp27 and Hsp70 in A549 cells. (PMID:16598923)
• HSP27 is linked to multi-drug resistance in cell line HepG2/VCR. (PMID:17524270)
• positive effect of Id-1 on TGF-beta1-induced cell motility was mediated through activation of MEK-ERK signaling pathway and subsequent phosphorylation of HSP27 (PMID:17916352)
• a cellular defense against dysregulated proteins, in the form of Hsp27 and alphaB-crystallin, might contribute to the cell cycle reentry seen in AD cells. (PMID:18061943)
• These data show that Hsp27 antagonizes Bax-mediated mitochondrial injury and apoptosis by promoting Akt activation via a PI3-kinase-dependent mechanism. (PMID:18299320)
• Upon heating at 43 degrees C, Hsp27 effectively suppresses myosin subfragment 1 aggregation, and this effect is enhanced by mutations mimicking Hsp27 phosphorylation. (PMID:18387368)
• In a large cohort of type 1 diabetic subjects, we found an independent association between serum HSP27 and distal symmetrical polyneuropathy. (PMID:18390793)
• These findings identify a novel pathway for vascular endothelial growth factor-induced HSP27 serine 82 phosphorylation via PKC-mediated PKD activation and direct phosphorylation of HSP27 by PKD. (PMID:18440775)
• HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion. (PMID:18471985)
• annexin II is a novel HSP27-interacted protein which is involved in UVC resistance in human cells (PMID:18494762)
• Mechanistic in vitro studies showed upregulated HSP27 expression and secretion in human macrophages treated with estrogen or acLDL. (PMID:18566345)
• In conclusion, despite the protective action against acute motor neuron injury, Hsp27 alone is not sufficient to protect against the chronic motor neuron injury due to the presence of mutant SOD1. (PMID:18624915)
• mRNA expressions of Hsp70, Hsp32 and Bax significantly increased in mononuclear blood cells after marathon running, whereas Hsp27 and Bad mRNA expression levels showed no significant changes. (PMID:18651163)
• Pint mutations in patients with type 2 diabetes and their families were studied. mitochondrial genes including np3316, np3394 and np3426 in the ND1 region and np3243 in the tRNA(Leu(UUR))were screened. (PMID:18701018)
• Overexpression of HSP27 in squamous cell carcinoma of the uterine cervix: a proteomic analysis using archival formalin-fixed, paraffin-embedded issues is reported. (PMID:18755499)
• HSP27 and HSP60 are predictors of biochemical recurrence of prostate cancer after radical prostatectomy. (PMID:19132982)
• show that Hsp27 and actin are in the same complex in cells and that Hsp27 is important for cell motility. (PMID:19224398)
• the differential expression patterns of alphaB-crystallin and Hsp27 indicate functional differences between these highly related proteins in placental tissues. (PMID:19238749)
• data show islet protection in mice by human HSP27 by mitigation of apoptosis, possibly through nuclear factor kappaB regulation. (PMID:19325007)
• Findings revealed a possible effect of HSP27 on apoptosis in metastatic HCC cells, in which HSP27 may regulate NF-kB pathway activation. (PMID:19331697)
• findings provide the first evidence that expanded ataxin-3 interferes with Hsp27 synthesis, which may contribute to the impairment of the cells’ ability to respond to stresses and trigger the progression of Machado-Joseph disease (PMID:19429074)
• Sodium salicylate can induce the expression of HSP27 in human lens epithelial cells. (PMID:19513626)
• PM induces ROS generation in human lung endothelium, resulting in oxidative stress-mediated EC barrier disruption via p38 MAPK- and HSP27-dependent pathways. (PMID:19520919)
• Overexpression of huHSP27 protects against hepatic injury and acute kidney injury associated with liver ischemia-reperfusion injury in mice. (PMID:19656912)
• 5-fluorouracil & carboplatin specifically induce expression of Hsp27 in hepatoma cells. siRNA knockdown of Hsp27 diminishes survival of drug-exposed cells. (PMID:19901540)
• Small interfering RNA-mediated silencing of heat shock protein 27 (HSP27) Increases chemosensitivity to paclitaxel by increasing production of reactive oxygen species in ovarian cancer. (PMID:19930842)
• HSP27 and p53 protein levels play a key role(s) in heat shock-mediated switch of glucose depreivation-induced necrosis to apoptosis. (PMID:20043073)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspb2	ENSDARG00000052450
mus_musculus	Hspb2	ENSMUSG00000038086
drosophila_melanogaster	Hsp22	FBGN0001223
drosophila_melanogaster	Hsp23	FBGN0001224
drosophila_melanogaster	Hsp26	FBGN0001225
drosophila_melanogaster	Hsp67Ba	FBGN0001227
drosophila_melanogaster	Hsp67Bc	FBGN0001229
drosophila_melanogaster	l(2)efl	FBGN0011296
drosophila_melanogaster	CG14207	FBGN0031037
caenorhabditis_elegans		WBGENE00002011
caenorhabditis_elegans		WBGENE00002015
caenorhabditis_elegans		WBGENE00002016
caenorhabditis_elegans		WBGENE00002017
caenorhabditis_elegans		WBGENE00002018
caenorhabditis_elegans		WBGENE00002019
caenorhabditis_elegans		WBGENE00002020
caenorhabditis_elegans		WBGENE00002023
caenorhabditis_elegans		WBGENE00008591
caenorhabditis_elegans		WBGENE00008592
caenorhabditis_elegans	hsp-12.1	WBGENE00011906

Paralogs (8): HSPB6 (ENSG00000004776), HSPB1 (ENSG00000106211), CRYAB (ENSG00000109846), HSPB8 (ENSG00000152137), CRYAA (ENSG00000160202), HSPB3 (ENSG00000169271), HSPB7 (ENSG00000173641), HSPB9 (ENSG00000260325)

Protein

Protein identifiers

Heat shock protein beta-2 — Q16082 (reviewed: Q16082)

Alternative names: DMPK-binding protein, Heat shock protein family B member 2

All UniProt accessions (1): Q16082

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the kinase DMPK.

Subunit / interactions. Interacts with DMPK; may enhance its kinase activity.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed preferentially in skeletal muscle and heart but not in the lens.

Similarity. Belongs to the small heat shock protein (HSP20) family.

RefSeq proteins (1): NP_001532* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001436	Alpha-crystallin/sHSP_animal	Family
IPR002068	A-crystallin/Hsp20_dom	Domain
IPR003090	Alpha-crystallin_N	Domain
IPR008978	HSP20-like_chaperone	Homologous_superfamily

Pfam: PF00011, PF00525

UniProt features (3 total): chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6F2R	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16082-F1	75.15	0.29

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371511	HSF1 activation
R-HSA-3371568	Attenuation phase
R-HSA-3371571	HSF1-dependent transactivation

MSigDB gene sets: 181 (showing top): MORF_RAGE, FXR_IR1_Q6, MORF_FLT1, TSENG_IRS1_TARGETS_UP, MODULE_16, FOXO1_01, CAGCTG_AP4_Q5, SP1_Q2_01, EVI1_05, GOBP_PROTEIN_MATURATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_FANCG, ZIC1_01, GOBP_PROTEIN_FOLDING

GO Biological Process (5): response to unfolded protein (GO:0006986), somatic muscle development (GO:0007525), response to heat (GO:0009408), protein refolding (GO:0042026), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (4): structural constituent of eye lens (GO:0005212), enzyme activator activity (GO:0008047), obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cellular response to heat stress	3
HSF1-dependent transactivation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
response to topologically incorrect protein	1
muscle structure development	1
response to stress	1
response to temperature stimulus	1
protein folding	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
structural molecule activity	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPB2	CYCS	P00001	989
HSPB2	HSPA4	P34932	989
HSPB2	PLEC	Q15149	954
HSPB2	HSPA8	P11142	933
HSPB2	HSP90AB1	P08238	926
HSPB2	AKT1	P31749	923
HSPB2	HSP90AA1	P07900	920
HSPB2	EIF4G1	Q04637	907
HSPB2	HSPA1A	P08107	896
HSPB2	HSPB8	Q9UJY1	891
HSPB2	HSPBAP1	Q96EW2	882
HSPB2	DAXX	Q9UER7	824
HSPB2	MAPKAPK2	P49137	821
HSPB2	CASP3	P42574	813
HSPB2	MAPKAPK5	Q8IW41	812

IntAct

172 interactions, top by confidence:

A	B	Type	Score
BAG3	HSPB2	psi-mi:“MI:0915”(physical association)	0.670
HSPB2	BAG3	psi-mi:“MI:0914”(association)	0.670
RFPL3	HSPB2	psi-mi:“MI:0915”(physical association)	0.600
CRYAB	HSPB2	psi-mi:“MI:0915”(physical association)	0.590
HSPB2	CRYAB	psi-mi:“MI:0915”(physical association)	0.590
CRYAB	HSPB2	psi-mi:“MI:0407”(direct interaction)	0.590
HSPB2	BICRAL	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	WWOX	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	MISP	psi-mi:“MI:0915”(physical association)	0.560
	HSPB2	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	SNX18	psi-mi:“MI:0915”(physical association)	0.560
PRR35	HSPB2	psi-mi:“MI:0915”(physical association)	0.560
TLX3	HSPB2	psi-mi:“MI:0915”(physical association)	0.560
VEZF1	HSPB2	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	KANK2	psi-mi:“MI:0915”(physical association)	0.560
HOXB9	HSPB2	psi-mi:“MI:0915”(physical association)	0.560
POGZ	HSPB2	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	BEX2	psi-mi:“MI:0915”(physical association)	0.560
LMO1	HSPB2	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	A1CF	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	PATZ1	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	LMO3	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	CEP19	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
APP	HSPB2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (157): ACTA1 (Two-hybrid), ACTB (Two-hybrid), ACTC1 (Two-hybrid), ACTG1 (Two-hybrid), CAPZA2 (Two-hybrid), CMYA5 (Two-hybrid), BGN (Two-hybrid), DCTN1 (Two-hybrid), ENO3 (Two-hybrid), FLNC (Two-hybrid), MYBPC3 (Two-hybrid), MYH6 (Two-hybrid), MYOM2 (Two-hybrid), RYR2 (Two-hybrid), TCAP (Two-hybrid)

ESM2 similar proteins: E2RDP2, O14526, O14558, O15197, O35878, O95382, P02512, P04792, P0C0K6, P0C5W1, P14602, P15991, P42929, P42930, P97541, Q00649, Q08DM2, Q13470, Q148F8, Q16082, Q2KHU9, Q2KIR4, Q3T033, Q3T149, Q4VYA0, Q5EBG6, Q5JR98, Q5JZY3, Q5RE82, Q5S1U1, Q6F5E8, Q6NY19, Q6P9Q4, Q6SJQ8, Q6ZW31, Q8C052, Q8CDY7, Q8N5L8, Q8TBH0, Q8TDZ2

Diamond homologs: O12984, O12988, O13224, O14558, O35878, O73919, O93591, P02470, P02472, P02474, P02475, P02476, P02477, P02478, P02479, P02480, P02482, P02483, P02484, P02485, P02486, P02487, P02488, P02489, P02492, P02493, P02494, P02497, P02498, P02499, P02500, P02501, P02502, P02503, P02504, P02505, P02506, P02507, P02508, P02509

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
Striated Muscle Contraction	7	27.4×	2e-06
Mitochondrial protein degradation	7	10.1×	4e-04
Respiratory electron transport	8	9.6×	2e-04
Peptide chain elongation	6	9.6×	2e-03
Muscle contraction	9	8.8×	1e-04
Platelet degranulation	6	6.7×	9e-03
Extracellular matrix organization	8	6.4×	2e-03
Innate Immune System	11	3.5×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
muscle filament sliding	5	52.7×	5e-06
striated muscle contraction	5	42.1×	1e-05
cardiac muscle contraction	9	36.1×	1e-09
ventricular cardiac muscle tissue morphogenesis	5	35.1×	2e-05
sarcomere organization	9	34.5×	1e-09
skeletal muscle contraction	6	30.6×	6e-06
response to hydrogen peroxide	5	23.4×	2e-04
glycolytic process	6	23.0×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2426878	NC_000011.9:g.(?111657121)(111922093_?)del	Pathogenic
2671625	Single allele	Pathogenic

SpliceAI

179 predictions. Top by Δscore:

Variant	Effect	Δscore
11:111913438:TAG:T	acceptor_loss	0.9900
11:111913439:AGGCC:A	acceptor_loss	0.9900
11:111912924:G:T	donor_loss	0.9800
11:111912925:T:G	donor_loss	0.9800
11:111913439:A:AG	acceptor_gain	0.9700
11:111913440:G:GG	acceptor_gain	0.9700
11:111912920:GAAG:G	donor_gain	0.9500
11:111913440:GGC:G	acceptor_gain	0.9400
11:111913439:AG:A	acceptor_gain	0.9200
11:111913440:GG:G	acceptor_gain	0.9200
11:111913440:GGCCT:G	acceptor_gain	0.9100
11:111912924:G:GG	donor_gain	0.8800
11:111913431:T:TA	acceptor_gain	0.8800
11:111913440:GGCC:G	acceptor_gain	0.8400
11:111913431:T:A	acceptor_loss	0.7800
11:111913576:TTCTG:T	acceptor_gain	0.7600
11:111913579:TG:T	acceptor_gain	0.7600
11:111913580:GG:G	acceptor_gain	0.7600
11:111913604:CG:C	acceptor_gain	0.7100
11:111913577:TCTGG:T	acceptor_gain	0.7000
11:111913601:A:AG	acceptor_gain	0.6600
11:111913602:G:GG	acceptor_gain	0.6600
11:111913585:TGAGC:T	acceptor_gain	0.6500
11:111913605:G:GC	acceptor_gain	0.6500
11:111912463:T:A	donor_gain	0.6300
11:111912921:A:T	donor_gain	0.6300
11:111913638:G:C	acceptor_gain	0.6200
11:111912462:G:A	donor_gain	0.6100
11:111913587:AGC:A	acceptor_gain	0.6100
11:111913599:C:CA	acceptor_gain	0.6100

AlphaMissense

1157 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:111913594:T:C	F83S	1.000
11:111913593:T:C	F83L	0.999
11:111913595:T:A	F83L	0.999
11:111913595:T:G	F83L	0.999
11:111913771:T:C	L142S	0.999
11:111913567:T:C	F74S	0.998
11:111913593:T:A	F83I	0.998
11:111913633:T:C	L96P	0.998
11:111913636:T:C	L97P	0.998
11:111913696:T:C	F117S	0.998
11:111913765:G:T	G140V	0.998
11:111913615:T:A	V90E	0.997
11:111913648:C:A	A101D	0.997
11:111913701:C:A	R119S	0.997
11:111913566:T:C	F74L	0.996
11:111913568:C:A	F74L	0.996
11:111913568:C:G	F74L	0.996
11:111913579:T:C	L78P	0.996
11:111913585:T:A	V80E	0.996
11:111913594:T:G	F83C	0.996
11:111913606:A:T	E87V	0.996
11:111913678:G:A	G111D	0.996
11:111913707:T:G	Y121D	0.996
11:111913714:T:A	L123Q	0.996
11:111913593:T:G	F83V	0.995
11:111913680:T:C	F112L	0.995
11:111913682:C:A	F112L	0.995
11:111913682:C:G	F112L	0.995
11:111913686:T:C	S114P	0.995
11:111913702:G:C	R119P	0.995

dbSNP variants (sampled 300 via entrez): RS1000792864 (11:111912487 G>A,C), RS1002278304 (11:111911708 T>A,C), RS1005927969 (11:111912862 G>A,T), RS1007388164 (11:111912519 A>C,G), RS1007419531 (11:111912729 C>A), RS1009555819 (11:111911322 A>G), RS1009985677 (11:111912075 G>T), RS1013636882 (11:111913304 T>C), RS1015016153 (11:111910755 A>G), RS1015504096 (11:111911049 G>A), RS1019113146 (11:111912179 T>C), RS1025054358 (11:111913587 A>T), RS1025704321 (11:111913950 G>A), RS1026457180 (11:111912620 G>A), RS1027718776 (11:111911067 C>G)

Disease associations

OMIM: gene MIM:602179 | disease phenotypes: MIM:608776

GenCC curated gene-disease

Mondo (1): ALG9-congenital disorder of glycosylation (MONDO:0012117)

Orphanet (1): ALG9-CDG (Orphanet:79328)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012227_630	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535750	Congenital disorder of glycosylation type 1L (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
4-(3,5-dimethoxystyryl)phenyl acetate	increases phosphorylation	1
FR900359	decreases phosphorylation	1
bisphenol A	increases expression	1
pirimicarb	decreases expression	1
linalool	increases expression	1
SB 203580	increases phosphorylation, decreases reaction	1
bifenthrin	decreases expression	1
N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases response to substance	1
Estradiol	affects expression	1
Fluorouracil	increases phosphorylation, decreases reaction	1
Malathion	increases expression	1
Selenium	decreases expression	1
Triclosan	decreases expression	1
Vincristine	decreases response to substance	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
tert-Butylhydroperoxide	decreases expression	1

Clinical trials (associated diseases)

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