SERPINB8

Summary

SERPINB8 (serpin family B member 8, HGNC:8952) is a protein-coding gene on chromosome 18q22.1, encoding Serpin B8 (P50452). Has an important role in epithelial desmosome-mediated cell-cell adhesion.

The protein encoded by this gene is a member of the ov-serpin family of serine protease inhibitors. The encoded protein is produced by platelets and can bind to and inhibit the function of furin, a serine protease involved in platelet functions. In addition, this protein has been found to enhance the mechanical stability of cell-cell adhesion in the skin, and defects in this gene have been associated with an autosomal-recessive form of exfoliative ichthyosis.

Source: NCBI Gene 5271 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peeling skin syndrome 5 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 108 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002640

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8952
Approved symbol	SERPINB8
Name	serpin family B member 8
Location	18q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CAP2
Ensembl gene	ENSG00000166401
Ensembl biotype	protein_coding
OMIM	601697
Entrez	5271

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000295211, ENST00000353706, ENST00000397985, ENST00000397988, ENST00000441827, ENST00000448851, ENST00000493661, ENST00000542677, ENST00000636430, ENST00000858461

RefSeq mRNA: 9 — MANE Select: NM_002640 NM_001031848, NM_001276490, NM_001348367, NM_001348368, NM_001348369, NM_001348370, NM_001366198, NM_002640, NM_198833

CCDS: CCDS11991, CCDS42442, CCDS62460, CCDS86678

Canonical transcript exons

ENST00000397985 — 7 exons

Exon	Start	End
ENSE00000670292	63985093	63985245
ENSE00001531067	63970081	63970170
ENSE00001896189	63986874	63989374
ENSE00003546250	63978299	63978476
ENSE00003573671	63979801	63979938
ENSE00003576294	63981721	63981838
ENSE00003663827	63983579	63983721

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 94.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.6657 / max 195.8905, expressed in 1607 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170666	9.6657	1607

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	94.28	gold quality
skin of leg	UBERON:0001511	93.91	gold quality
mononuclear cell	CL:0000842	93.67	gold quality
leukocyte	CL:0000738	93.41	gold quality
skin of abdomen	UBERON:0001416	92.29	gold quality
zone of skin	UBERON:0000014	91.25	gold quality
lower esophagus mucosa	UBERON:0035834	90.84	gold quality
esophagus mucosa	UBERON:0002469	89.02	gold quality
granulocyte	CL:0000094	88.86	gold quality
gall bladder	UBERON:0002110	87.04	gold quality
islet of Langerhans	UBERON:0000006	86.25	gold quality
gingival epithelium	UBERON:0001949	84.88	silver quality
descending thoracic aorta	UBERON:0002345	84.87	gold quality
tibial artery	UBERON:0007610	84.44	gold quality
popliteal artery	UBERON:0002250	84.42	gold quality
artery	UBERON:0001637	83.87	gold quality
aorta	UBERON:0000947	83.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.44	gold quality
gingiva	UBERON:0001828	83.32	silver quality
calcaneal tendon	UBERON:0003701	83.25	gold quality
esophagus	UBERON:0001043	83.20	gold quality
upper lobe of left lung	UBERON:0008952	83.09	gold quality
thoracic aorta	UBERON:0001515	82.99	gold quality
stromal cell of endometrium	CL:0002255	82.95	gold quality
ascending aorta	UBERON:0001496	82.82	gold quality
right lung	UBERON:0002167	82.58	gold quality
left coronary artery	UBERON:0001626	82.24	gold quality
upper lobe of lung	UBERON:0008948	82.06	gold quality
right coronary artery	UBERON:0001625	82.02	gold quality
right adrenal gland cortex	UBERON:0035827	81.85	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	18.75
E-ENAD-17	no	172.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting SERPINB8, 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-4481	100.00	66.42	1669
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-4652-5P	96.46	64.22	553
HSA-MIR-6823-5P	96.26	65.69	919

Literature-anchored findings (GeneRIF, showing 5)

• PI8 is released by platelets and controls functional responses (PMID:16493485)
• Data show that SERPINB8 is expressed in normal neuroendocrine cells of several organs as well as in neuroendocrine tumors of the pancreas, where it can be used as an additional diagnostic immunohistochemical marker. (PMID:19188865)
• report of mutations in SERPINB8 that are associated with exfoliative ichthyosis and provide evidence that SERPINB8 contributes to the mechanical stability of intercellular adhesions in the epidermis (PMID:27476651)
• SERPINB8 and furin regulate ITGAX expression and affect the proliferation and invasion of melanoma cells. (PMID:36134483)
• Inhibition of Infectious HIV-1 Production by Rerouting the Cellular Furin Inhibitor Serpin B8. (PMID:37272794)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	serpinb1l3	ENSDARG00000014556
danio_rerio	zgc:173729	ENSDARG00000057263
danio_rerio	serpinb14	ENSDARG00000091801
danio_rerio	serpinb1l1	ENSDARG00000095830
danio_rerio	serpinb1l4	ENSDARG00000096888
mus_musculus	Serpinb8	ENSMUSG00000026315
rattus_norvegicus	Serpinb8	ENSRNOG00000002396

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Serpin B8 — P50452 (reviewed: P50452)

Alternative names: Cytoplasmic antiproteinase 2, Peptidase inhibitor 8

All UniProt accessions (6): A0A087WTX6, A0A1B0GU38, C9JTJ8, P50452, C9JVA8, H7BXK7

UniProt curated annotations — full annotation on UniProt →

Function. Has an important role in epithelial desmosome-mediated cell-cell adhesion.

Subcellular location. Cytoplasm.

Disease relevance. Peeling skin syndrome 5 (PSS5) [MIM:617115] A form of peeling skin syndrome, a genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels. PSS5 patients manifest hyperkeratosis and superficial peeling of areas of the palmar and dorsal faces of hands and feet. Additional variable features include erythema, superficial scaling of forearms and legs and diffuse yellowish hyperkeratotic palmoplantar plaques. PSS5 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the serpin family. Ov-serpin subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P50452-1	1	yes
P50452-2	2
P50452-3	3

RefSeq proteins (9): NP_001027018, NP_001263419, NP_001335296, NP_001335297, NP_001335298, NP_001335299, NP_001353127, NP_002631, NP_942130 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (8 total): sequence variant 4, splice variant 2, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50452-F1	91.48	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 339–340 (reactive bond)

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-75205	Dissolution of Fibrin Clot
R-HSA-109582	Hemostasis

MSigDB gene sets: 436 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, NAGASHIMA_NRG1_SIGNALING_UP, PATIL_LIVER_CANCER

GO Biological Process (2): negative regulation of endopeptidase activity (GO:0010951), epithelial cell-cell adhesion (GO:0090136)

GO Molecular Function (3): serine-type endopeptidase inhibitor activity (GO:0004867), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
endopeptidase activity	1
negative regulation of peptidase activity	1
regulation of endopeptidase activity	1
cell-cell adhesion	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular anatomical structure	1
cytoplasm	1
external encapsulating structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

804 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINB8	ZNF816	Q0VGE8	628
SERPINB8	CSMD1	Q96PZ7	535
SERPINB8	TNIP1	Q15025	435
SERPINB8	GZMB	P10144	420
SERPINB8	PRF1	P14222	407
SERPINB8	ERAP1	Q9NZ08	406
SERPINB8	PTTG1	O95997	384
SERPINB8	GJB2	P29033	375
SERPINB8	IL13	P35225	374
SERPINB8	IFNG	P01579	372
SERPINB8	PI3	P19957	370
SERPINB8	SERPINB6	P35237	366
SERPINB8	TNF	P01375	364
SERPINB8	CD4	P01730	359
SERPINB8	PROZ	P22891	357

IntAct

77 interactions, top by confidence:

A	B	Type	Score
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
CDKL5	SERPINB8	psi-mi:“MI:0915”(physical association)	0.560
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
SERPINB8	TOX4	psi-mi:“MI:0914”(association)	0.530
NHLH2	AP3B1	psi-mi:“MI:0914”(association)	0.530
NDUFS5	NDUFS4	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530
SPICE1	SERPINB2	psi-mi:“MI:0914”(association)	0.530
FANCD2OS	CNOT1	psi-mi:“MI:0914”(association)	0.530
TAS2R8	SERPINB8	psi-mi:“MI:0915”(physical association)	0.400
ATN1	SERPINB8	psi-mi:“MI:0915”(physical association)	0.400
WDR33	SERPINB8	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
GPATCH2L	A2ML1	psi-mi:“MI:0914”(association)	0.350
FCF1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
ZRSR2	U2SURP	psi-mi:“MI:0914”(association)	0.350
CDKL5	DHX16	psi-mi:“MI:0914”(association)	0.350
SERPINB6	PLAT	psi-mi:“MI:0914”(association)	0.350
PRKCE	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
TIFAB	DDX3X	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
ANKRD39	UBA6	psi-mi:“MI:0914”(association)	0.350
VAMP4	NBAS	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (98): SERPINB8 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), CTH (Co-fractionation), ITPA (Co-fractionation), SERPINB8 (Co-fractionation), SERPINB8 (Co-fractionation), SERPINB8 (Co-fractionation), SERPINB8 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), NONO (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS)

ESM2 similar proteins: O00394, O02739, O08800, O54757, O54758, O54759, O54760, O54761, O54762, O54763, P01009, P01010, P05619, P07758, P12725, P17475, P22324, P22325, P22599, P23035, P29508, P30740, P34955, P35237, P38029, P48594, P50447, P50452, P50453, P80229, P97277, Q00896, Q00897, Q00898, Q09055, Q1JPB0, Q4G075, Q4R3G2, Q52L45, Q5BIR5

Diamond homologs: A0A090BX51, A0A0K8RCY5, A0A0K8RJ89, A0A0K8RJV9, A5PJK0, A9RA96, B0CMB0, B1MTB7, B1MTC3, B2KI30, B3RFC3, B4USX2, E2RVI8, O02739, O08800, O35684, O54757, O54758, O54759, O54760, O73790, O73860, O75635, O75830, P01008, P01011, P01012, P01014, P05120, P05619, P12388, P17475, P19104, P22323, P22325, P22922, P23035, P29508, P29524, P30740

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	58
Likely benign	20
Benign	21

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
254199	NM_002640.4(SERPINB8):c.2T>C (p.Met1Thr)	Pathogenic
2585175	NM_002640.4(SERPINB8):c.270del (p.Asn90fs)	Likely pathogenic
3780595	NM_002640.4(SERPINB8):c.820G>T (p.Glu274Ter)	Likely pathogenic

SpliceAI

1018 predictions. Top by Δscore:

Variant	Effect	Δscore
18:63970168:G:GT	donor_gain	1.0000
18:63979939:G:GG	donor_gain	1.0000
18:63981712:T:TA	acceptor_gain	1.0000
18:63981716:TGCAG:T	acceptor_gain	1.0000
18:63981717:GCAGG:G	acceptor_gain	1.0000
18:63981718:CAGGA:C	acceptor_gain	1.0000
18:63981719:A:AG	acceptor_gain	1.0000
18:63981719:AG:A	acceptor_gain	1.0000
18:63981719:AGGAC:A	acceptor_gain	1.0000
18:63981720:G:A	acceptor_gain	1.0000
18:63981720:G:GA	acceptor_gain	1.0000
18:63981720:GGA:G	acceptor_gain	1.0000
18:63981720:GGAC:G	acceptor_gain	1.0000
18:63981720:GGACT:G	acceptor_gain	1.0000
18:63981801:G:GT	donor_gain	1.0000
18:63981835:GAAG:G	donor_gain	1.0000
18:63981836:AAGGT:A	donor_loss	1.0000
18:63981837:AGGTG:A	donor_loss	1.0000
18:63981838:GGTG:G	donor_loss	1.0000
18:63981839:G:GG	donor_gain	1.0000
18:63981839:GT:G	donor_loss	1.0000
18:63985089:TTAG:T	acceptor_loss	1.0000
18:63985090:TA:T	acceptor_loss	1.0000
18:63985091:A:AG	acceptor_gain	1.0000
18:63985092:G:GG	acceptor_gain	1.0000
18:63985092:G:GT	acceptor_loss	1.0000
18:63985243:GTG:G	donor_gain	1.0000
18:63985246:G:GA	donor_loss	1.0000
18:63985246:G:GG	donor_gain	1.0000
18:63985247:TAAGC:T	donor_loss	1.0000

AlphaMissense

2502 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:63983665:T:A	W171R	0.995
18:63983665:T:C	W171R	0.995
18:63983677:T:C	F175L	0.993
18:63983679:T:A	F175L	0.993
18:63983679:T:G	F175L	0.993
18:63983667:G:C	W171C	0.989
18:63983667:G:T	W171C	0.989
18:63987210:T:C	F353L	0.988
18:63987212:T:A	F353L	0.988
18:63987212:T:G	F353L	0.988
18:63983707:T:C	F185L	0.984
18:63983709:T:A	F185L	0.984
18:63983709:T:G	F185L	0.984
18:63978408:A:C	S34R	0.982
18:63978410:C:A	S34R	0.982
18:63978410:C:G	S34R	0.982
18:63983666:G:C	W171S	0.979
18:63987027:T:C	F292L	0.979
18:63987029:T:A	F292L	0.979
18:63987029:T:G	F292L	0.979
18:63987135:G:C	A328P	0.979
18:63985172:T:C	L216P	0.977
18:63978444:G:C	A46P	0.976
18:63983708:T:C	F185S	0.976
18:63985217:T:C	L231P	0.976
18:63987192:T:C	F347L	0.976
18:63987194:C:A	F347L	0.976
18:63987194:C:G	F347L	0.976
18:63979909:T:C	F93L	0.975
18:63979911:T:A	F93L	0.975

dbSNP variants (sampled 300 via entrez): RS1000006505 (18:63983258 G>A), RS1000052707 (18:63991132 A>G), RS1000081665 (18:64008008 A>C), RS1000103370 (18:63990870 A>G), RS1000178750 (18:64012810 G>A), RS1000190907 (18:64013048 A>C), RS1000193824 (18:64007831 C>A,T), RS1000230539 (18:63984493 G>A), RS1000281121 (18:63996276 T>C), RS1000324313 (18:64019077 T>C), RS1000341009 (18:63978236 A>G), RS1000375268 (18:64002041 A>G), RS1000401719 (18:64018780 C>T), RS1000605664 (18:63995395 C>G), RS1000642595 (18:63971848 C>A)

Disease associations

OMIM: gene MIM:601697 | disease phenotypes: MIM:617115

GenCC curated gene-disease

Disease	Classification	Inheritance
peeling skin syndrome 5	Strong	Autosomal recessive
exfoliative ichthyosis	Supportive	Autosomal recessive

Mondo (2): peeling skin syndrome 5 (MONDO:0014923), exfoliative ichthyosis (MONDO:0017339)

Orphanet (0):

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000962	Hyperkeratosis
HP:0000969	Edema
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001727	Thromboembolic stroke
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy
HP:0003457	EMG abnormality
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0004755	Supraventricular tachycardia
HP:0011463	Childhood onset
HP:0011675	Arrhythmia
HP:0012378	Fatigue
HP:0012666	Severely reduced left ventricular ejection fraction
HP:0012764	Orthopnea
HP:0025092	Epidermal acanthosis
HP:0025169	Left ventricular systolic dysfunction
HP:0040189	Scaling skin
HP:0100578	Lipoatrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001621_9	Airflow obstruction	7.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725085 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178935: Inhibition of SERPINB8 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, increases abundance	4
Benzo(a)pyrene	affects methylation, increases expression	4
Cadmium Chloride	increases abundance, increases expression	4
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression	3
Cisplatin	affects cotreatment, decreases expression, increases expression	3
Air Pollutants	increases expression, increases abundance	2
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
Cadmium	increases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	affects expression, decreases expression	2
Zinc	affects cotreatment, increases expression, decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
1-nitropyrene	increases expression	1
benazol P	affects expression	1
pentanal	increases expression	1
dinophysistoxin 1	increases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697665	Binding	Inhibition of SERPINB8 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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