SERPINB7

Summary

SERPINB7 (serpin family B member 7, HGNC:13902) is a protein-coding gene on chromosome 18q21.33, encoding Serpin B7 (O75635). Might function as an inhibitor of Lys-specific proteases.

This gene encodes a member of a family of proteins which function as protease inhibitors. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8710 — RefSeq curated summary.

At a glance

• Gene–disease (curated): palmoplantar keratoderma, Nagashima type (Definitive, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 119 total — 8 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 14
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_003784

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13902
Approved symbol	SERPINB7
Name	serpin family B member 7
Location	18q21.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166396
Ensembl biotype	protein_coding
OMIM	603357
Entrez	8710

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000336429, ENST00000398019, ENST00000425392, ENST00000431370, ENST00000447428, ENST00000540675, ENST00000546027, ENST00000894156, ENST00000894157

RefSeq mRNA: 4 — MANE Select: NM_003784 NM_001040147, NM_001261830, NM_001261831, NM_003784

CCDS: CCDS11988, CCDS58633

Canonical transcript exons

ENST00000398019 — 8 exons

Exon	Start	End
ENSE00000914923	63792393	63792443
ENSE00000914925	63793161	63793277
ENSE00001102586	63796266	63796383
ENSE00001102589	63782355	63782540
ENSE00001102605	63800866	63801012
ENSE00001102608	63798604	63798746
ENSE00001531190	63804237	63805370
ENSE00001531191	63775418	63775716

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 97.19.

FANTOM5 (CAGE): breadth broad, TPM avg 6.7107 / max 606.3927, expressed in 555 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170606	3.0905	381
170598	2.2892	441
170599	0.2353	81
170597	0.2173	73
170602	0.1779	48
170600	0.1587	67
170593	0.1381	24
170608	0.0969	30
170601	0.0892	37
208582	0.0494	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	97.19	gold quality
skin of leg	UBERON:0001511	95.76	gold quality
penis	UBERON:0000989	95.71	gold quality
skin of abdomen	UBERON:0001416	95.06	gold quality
zone of skin	UBERON:0000014	94.92	gold quality
upper leg skin	UBERON:0004262	93.69	gold quality
skin of hip	UBERON:0001554	86.86	gold quality
epithelium of nasopharynx	UBERON:0001951	86.37	gold quality
mammalian vulva	UBERON:0000997	86.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.18	gold quality
bronchial epithelial cell	CL:0002328	84.28	gold quality
nipple	UBERON:0002030	83.95	gold quality
amniotic fluid	UBERON:0000173	81.79	gold quality
epithelium of bronchus	UBERON:0002031	78.43	gold quality
bronchus	UBERON:0002185	77.10	gold quality
islet of Langerhans	UBERON:0000006	74.21	gold quality
stromal cell of endometrium	CL:0002255	74.10	gold quality
oral cavity	UBERON:0000167	71.46	gold quality
type B pancreatic cell	CL:0000169	70.52	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	70.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	69.55	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.91	gold quality
tongue squamous epithelium	UBERON:0006919	66.89	gold quality
pancreatic ductal cell	CL:0002079	65.87	silver quality
gingiva	UBERON:0001828	65.00	silver quality
endometrium epithelium	UBERON:0004811	64.92	gold quality
cervix epithelium	UBERON:0004801	63.62	gold quality
epithelial cell of pancreas	CL:0000083	63.46	gold quality
tonsil	UBERON:0002372	63.20	gold quality
gingival epithelium	UBERON:0001949	62.76	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-10	no	793.39
E-ANND-3	no	4.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1

miRNA regulators (miRDB)

47 targeting SERPINB7, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
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-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-888-5P	99.30	70.15	1855

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 33)

• Mesangial cell-predominant gene, megsin. Genetic manipulation of megsin engenders two elementary mesangial lesions, mesangial expansion and an increase in the number of mesangial cells. (PMID:12386281)
• One positive regulatory motif, an incomplete activator protein-1 binding motif (CTGATTCAC) within the -120 to -112 region. This cis-acting element in the 5’-flanking region of megsin is involved in the activation of the megsin gene in mesangial cells. (PMID:12397041)
• Megsin has a role in susceptibility to immunoglobulin A nephropathy (PMID:15213261)
• in transgenic rats, overexpression of human megsin, a recently discovered serpin located in the kidney, produces renal and pancreatic lesions characteristic of serpinopathies (PMID:15788472)
• In this Chinese population, the 2093C-2180T haplotype at the 3’UTR of MEGSIN gene is associated with more severe forms of IgA nephropathy, and more rapid disease progression (PMID:16431886)
• The polymorphism of megsin A23167G is associated with susceptibility and progression of IgA nephropathy in Chinese population. GG genotype is associated with severe histological lesions and progression of the disease. (PMID:16550745)
• A267G in 5’-untranslated region within the exon of megsin may be one of the substantial genetic basis for differentiating “deficiency of liver yin and kidney yin” syndrome and “deficiency of qi and yin” syndrome in primary immunoglobulin A nephropathy. (PMID:18471408)
• study found out that the megsin TT haplotype (defined as T-2093, T-2180 alleles) could play a protective role in the progression of IgA nephropathy (PMID:18498720)
• recombinant megsin did not affect the mRNA expressions of TGF- and PAI-1, and did not modify the enzymatic activity of PAI-1 (PMID:18580857)
• Megsin 2093T-2180C haplotype at the 3’ untranslated region is associated with poor renal survival in Korean IgA nephropathy patients. (PMID:18793525)
• All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in palmoplantar keratosis skin. (PMID:24207119)
• study reports on seven unrelated Chinese patients with Nagashima-Type Palmoplantar Keratosis with four underlying SERPINB7 mutations, of which one is a recurrent variant (c.796C>T) (PMID:24514002)
• megsin 2093C/T C allele may be genetic marker for IgA nephropathy susceptibility [review] (PMID:24575807)
• These data clearly provide further evidence that NPPK is caused by loss-of-function mutations in SERPINB7. (PMID:24773080)
• The mean concentration of serpin B7 at 28-32 weeks was 1.5-fold higher in women with subsequent preterm deliveries compared to controls. (PMID:24954659)
• Megsin 2093C/T TT genotype, and C25663G G allele and GG genotype were associated with the risk of IgAN in Asian population (PMID:25007157)
• Results show splice variants from the two recurrent splice-site mutations in SERPINB7, provide evidence for the pathogenicity of the mutations and suggest an in-frame deletion of exon 3 may cause NPPK and that the CD-loop could affect SERPINB7 function (PMID:25940237)
• Recessive missense mutation of SERPINB7 gene was found in Japanese families diagnosed with palmoplantar keratosis. (PMID:26763456)
• These results indicate that megsin gene variants may play a role in the severity, development, and/or progression of IgAN in Northwest Chinese population (PMID:26871801)
• Direct sequencing of SERPINB7 revealed five homozygous founder mutations (c.796C>T) and four compound heterozygous mutations in nine patients, including one novel mutation (c.122_127delTGGTCC). (PMID:27666198)
• Case Report: striate palmoplantar keratoderma showing transgrediens in a patient with heterozygote nonsense mutations in DSG1 and SERPINB7. (PMID:27786350)
• SERPINB7 mutations are related strictly to the PPKN phenotype. Our study indicates that screening for SERPINB7 mutations is useful to distinguish PPKN from other PPK types and from non-PPK keratinizing diseases with palmoplantar skin lesions. (PMID:28211129)
• mutant SERPINB7 mRNAs harboring r.796c>u were degraded by nonsense-mediated mRNA decay. Furthermore, the truncated SERPINB7 protein was degraded via a proteasome-mediated pathway (PMID:29106929)
• SERPINB7 may be a valuable candidate for further studies. In the present study, a method for identifying novel key pathogenic skinspecific molecules is presented, which may be used for investigating and treating psoriasis. (PMID:30592269)
• Nagashima-type palmoplantar keratosis in Finland caused by a SERPINB7 founder mutation. (PMID:31706940)
• SERPINB7 novel mutation in Chinese patients with Nagashima-type palmoplantar keratosis and cases associated with atopic dermatitis. (PMID:32406097)
• Updated allele frequencies of SERPINB7 founder mutations in Asian patients with Nagashima-type palmoplantar keratosis/keratoderma. (PMID:34334259)
• Acral peeling in Nagashima type palmo-plantar keratosis patients reveals the role of serine protease inhibitor B 7 in keratinocyte adhesion. (PMID:34379845)
• Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis. (PMID:34454985)
• Two novel mutations of SERPINB7 in eight cases of Nagashima-type palmoplantar keratosis in the Chinese population. (PMID:35178744)
• SerpinB7 deficiency contributes to development of psoriasis via calcium-mediated keratinocyte differentiation dysfunction. (PMID:35864103)
• SERPINB7 mutation causes Nagashima-type palmoplantar keratosis and its spatiotemporal expression in zebrafish. (PMID:36772997)
• Potential digenic inheritance of SERPINB7 and SERPINA12 variants in Chinese patients with Nagashima-type palmoplantar keratosis. (PMID:38529670)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpinb7	ENSMUSG00000067001
rattus_norvegicus	Serpinb7	ENSRNOG00000002555

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), SERPINB8 (ENSG00000166401), 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 B7 — O75635 (reviewed: O75635)

Alternative names: Megsin, TP55

All UniProt accessions (4): A0A1B0GX82, C9JA68, C9JM00, O75635

UniProt curated annotations — full annotation on UniProt →

Function. Might function as an inhibitor of Lys-specific proteases. Might influence the maturation of megakaryocytes via its action as a serpin.

Subcellular location. Cytoplasm.

Tissue specificity. Predominantly expressed in mesangial cells. Expressed in the epidermis of the whole body.

Disease relevance. Keratoderma, palmoplantar, Nagashima type (PPKN) [MIM:615598] An autosomal recessive, non-syndromic, diffuse palmoplantar keratosis characterized by well-demarcated diffuse erythematous hyperkeratosis expanding onto the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis is mild and non-progressive. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O75635-1	1	yes
O75635-2	2

RefSeq proteins (4): NP_001035237, NP_001248759, NP_001248760, NP_003775* (*=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 (7 total): modified residue 2, chain 1, site 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75635-F1	89.91	0.77

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): 347–348 (reactive bond)

Post-translational modifications (2): 217, 223

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GGGTGGRR_PAX4_03, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_CELL_PROLIFERATION_INVOLVED_IN_KIDNEY_DEVELOPMENT, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CYTOKINE_PRODUCTION, GOBP_GLOMERULUS_DEVELOPMENT, MODULE_99, TGANTCA_AP1_C, GOBP_POSITIVE_REGULATION_OF_TRANSFORMING_GROWTH_FACTOR_BETA_PRODUCTION, GOBP_RENAL_SYSTEM_VASCULATURE_DEVELOPMENT, IK2_01, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT, GOBP_NEPHRON_DEVELOPMENT

GO Biological Process (4): positive regulation of transforming growth factor beta1 production (GO:0032914), positive regulation of collagen biosynthetic process (GO:0032967), positive regulation of glomerular mesangial cell proliferation (GO:0072126), positive regulation of platelet-derived growth factor production (GO:0090362)

GO Molecular Function (2): serine-type endopeptidase inhibitor activity (GO:0004867), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transforming growth factor beta1 production	1
regulation of transforming growth factor beta1 production	1
positive regulation of transforming growth factor beta production	1
positive regulation of biosynthetic process	1
positive regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
glomerular mesangial cell proliferation	1
regulation of glomerular mesangial cell proliferation	1
positive regulation of cell proliferation involved in kidney development	1
positive regulation of cytokine production	1
platelet-derived growth factor production	1
regulation of platelet-derived growth factor production	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1020 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINB7	PLEKHH2	Q8IVE3	662
SERPINB7	ELMO1	Q92556	611
SERPINB7	NEDD4L	Q96PU5	548
SERPINB7	PON1	P27169	494
SERPINB7	ACE	P12821	466
SERPINB7	F5H3C5	F5H3C5	425
SERPINB7	SOD2	P04179	425
SERPINB7	AAGAB	Q6PD74	400
SERPINB7	SPRR4	Q96PI1	400
SERPINB7	SLURP1	P55000	398
SERPINB7	IL1RN	P18510	398
SERPINB7	PLG	P00747	389
SERPINB7	HFE	Q30201	387
SERPINB7	DSC1	Q08554	381
SERPINB7	ALB	P02768	380
SERPINB7	C5orf46	Q6UWT4	380

IntAct

73 interactions, top by confidence:

A	B	Type	Score
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
MCL1	PRKAB2	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
KIR3DS1	PPL	psi-mi:“MI:0914”(association)	0.530
GDF5	SERPINB7	psi-mi:“MI:0914”(association)	0.530
NONO	SERPINB7	psi-mi:“MI:0914”(association)	0.530
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
PI4KA	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
PLK2	ANKRD28	psi-mi:“MI:0914”(association)	0.350
NONO	GYG2	psi-mi:“MI:0914”(association)	0.350
KLHL11	PIPSL	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
PI4KAP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
TEFM	A2ML1	psi-mi:“MI:0914”(association)	0.350
LRRC10	A2ML1	psi-mi:“MI:0914”(association)	0.350
GABPA	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS)

ESM2 similar proteins: A0A090BX51, A0A0K8RCY5, A0A0K8RJ89, A0A0K8RJV9, A0A7H0DNF9, B3RFC3, E2RVI8, O73860, O75635, P01008, P01012, P01014, P05120, P07092, P07093, P07385, P0DSW3, P12388, P13909, P14754, P15059, P19104, P20961, P22777, P22922, P42926, P50449, P68565, P68566, P79335, P80034, Q06B72, Q06B74, Q06B75, Q07235, Q27085, Q27086, Q5MGH0, Q5R5A3, Q6J201

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

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	2
Uncertain significance	70
Likely benign	15
Benign	18

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
102446	NM_003784.4(SERPINB7):c.796C>T (p.Arg266Ter)	Pathogenic
102447	NM_003784.4(SERPINB7):c.218_219delinsTAAACTTTACCT (p.Gln73fs)	Pathogenic
102448	NM_003784.4(SERPINB7):c.455-1G>A	Pathogenic
1323576	NM_003784.4(SERPINB7):c.157C>T (p.Gln53Ter)	Pathogenic
1333198	NM_003784.4(SERPINB7):c.650_653del (p.Ser217fs)	Pathogenic
157566	NM_003784.4(SERPINB7):c.522dup (p.Val175fs)	Pathogenic
3675005	NM_003784.4(SERPINB7):c.408del (p.Asp137fs)	Pathogenic
3766056	NM_003784.4(SERPINB7):c.455G>T (p.Gly152Val)	Pathogenic
3049966	NM_003784.4(SERPINB7):c.54_55del (p.Glu18fs)	Likely pathogenic
3723186	NM_003784.4(SERPINB7):c.336+2T>G	Likely pathogenic

SpliceAI

1217 predictions. Top by Δscore:

Variant	Effect	Δscore
18:63782353:A:AG	acceptor_gain	1.0000
18:63782353:AG:A	acceptor_gain	1.0000
18:63782353:AGGCT:A	acceptor_gain	1.0000
18:63782354:G:GT	acceptor_gain	1.0000
18:63782354:GG:G	acceptor_gain	1.0000
18:63782354:GGC:G	acceptor_gain	1.0000
18:63782354:GGCT:G	acceptor_gain	1.0000
18:63782354:GGCTG:G	acceptor_gain	1.0000
18:63782536:ATAAG:A	donor_loss	1.0000
18:63782538:AAGG:A	donor_loss	1.0000
18:63782541:G:GA	donor_loss	1.0000
18:63782542:T:A	donor_loss	1.0000
18:63792391:A:AG	acceptor_gain	1.0000
18:63792392:G:GG	acceptor_gain	1.0000
18:63793153:A:AG	acceptor_gain	1.0000
18:63793159:A:AG	acceptor_gain	1.0000
18:63793160:G:GG	acceptor_gain	1.0000
18:63793160:GT:G	acceptor_gain	1.0000
18:63793160:GTC:G	acceptor_gain	1.0000
18:63793160:GTCA:G	acceptor_gain	1.0000
18:63793276:AGG:A	donor_loss	1.0000
18:63793277:GGTA:G	donor_loss	1.0000
18:63793278:G:C	donor_loss	1.0000
18:63793279:T:G	donor_loss	1.0000
18:63796261:TATAG:T	acceptor_loss	1.0000
18:63796262:A:AG	acceptor_gain	1.0000
18:63796263:TA:T	acceptor_loss	1.0000
18:63796264:A:AG	acceptor_gain	1.0000
18:63796264:A:G	acceptor_loss	1.0000
18:63796264:AG:A	acceptor_gain	1.0000

AlphaMissense

2538 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:63798690:T:A	W181R	0.994
18:63798690:T:C	W181R	0.994
18:63798702:T:C	F185L	0.993
18:63798704:C:A	F185L	0.993
18:63798704:C:G	F185L	0.993
18:63798692:G:C	W181C	0.991
18:63798692:G:T	W181C	0.991
18:63804573:T:C	F361L	0.989
18:63804575:C:A	F361L	0.989
18:63804575:C:G	F361L	0.989
18:63798732:T:C	F195L	0.985
18:63798734:C:A	F195L	0.985
18:63798734:C:G	F195L	0.985
18:63798703:T:C	F185S	0.980
18:63798703:T:G	F185C	0.980
18:63782472:A:C	S34R	0.979
18:63782474:C:A	S34R	0.979
18:63782474:C:G	S34R	0.979
18:63793248:T:C	F103L	0.978
18:63793250:T:A	F103L	0.978
18:63793250:T:G	F103L	0.978
18:63804556:T:C	F355S	0.978
18:63800948:T:A	L227H	0.977
18:63798691:G:C	W181S	0.975
18:63798733:T:C	F195S	0.975
18:63800984:T:A	V239D	0.974
18:63804562:C:A	A357D	0.974
18:63800948:T:C	L227P	0.972
18:63800954:T:C	L229P	0.972
18:63804265:T:C	L258P	0.971

dbSNP variants (sampled 300 via entrez): RS1000010811 (18:63782938 A>G), RS1000107587 (18:63791673 C>T), RS1000116737 (18:63757757 A>G,T), RS1000117081 (18:63795043 A>T), RS1000142052 (18:63762162 G>A), RS1000192725 (18:63758846 G>A), RS1000234753 (18:63767420 A>G), RS1000257715 (18:63772744 A>T), RS1000279614 (18:63788566 T>C), RS1000360317 (18:63778367 A>C), RS1000385945 (18:63783829 T>A,G), RS1000411050 (18:63778004 C>T), RS1000419161 (18:63761339 A>T), RS1000445987 (18:63799824 T>C), RS1000486009 (18:63752108 A>G)

Disease associations

OMIM: gene MIM:603357 | disease phenotypes: MIM:615598

GenCC curated gene-disease

Disease	Classification	Inheritance
palmoplantar keratoderma, Nagashima type	Definitive	Autosomal recessive

Mondo (1): palmoplantar keratoderma, Nagashima type (MONDO:0014272)

Orphanet (1): Palmoplantar keratoderma, Nagashima type (Orphanet:140966)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000972	Palmoplantar hyperkeratosis
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0007410	Palmoplantar hyperhidrosis
HP:0011463	Childhood onset
HP:0025080	Orthokeratotic hyperkeratosis
HP:0025092	Epidermal acanthosis
HP:0025114	Hypergranulosis
HP:0032007	Maceration

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004977_2	Hen’s egg allergy	8.000000e-08
GCST004979_2	Food allergy	2.000000e-08
GCST005168_5	Systolic blood pressure	6.000000e-06
GCST007797_9	Asthma onset (childhood vs adult)	7.000000e-08
GCST007798_107	Asthma	1.000000e-06
GCST007800_47	Asthma (childhood onset)	8.000000e-18
GCST007994_21	Asthma (age of onset)	5.000000e-08
GCST007995_7	Asthma (childhood onset)	3.000000e-16
GCST008916_98	Asthma	2.000000e-09
GCST009720_71	Asthma	4.000000e-09
GCST010042_34	Asthma	3.000000e-09
GCST010043_42	Asthma	2.000000e-08
GCST010984_44	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	5.000000e-23
GCST010985_40	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	6.000000e-23
GCST90014325_69	Asthma	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007018	egg allergy measurement
EFO:0007016	food allergy measurement
EFO:0006335	systolic blood pressure
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression, affects expression	3
bisphenol A	decreases expression, decreases reaction, increases abundance	2
sodium arsenite	increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Formaldehyde	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
dimethylarsinous acid	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
NSC 689534	increases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	increases methylation	1
Camptothecin	increases expression	1

Clinical trials (associated diseases)

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