ZPBP2

Summary

ZPBP2 (zona pellucida binding protein 2, HGNC:20678) is a protein-coding gene on chromosome 17q21.1, encoding Zona pellucida-binding protein 2 (Q6X784). Is implicated in sperm-oocyte interaction during fertilization.

Predicted to be involved in acrosome assembly and binding activity of sperm to zona pellucida. Predicted to act upstream of or within obsolete membrane lipid catabolic process; regulation of gene expression; and sphingolipid metabolic process. Located in nucleus. Implicated in asthma and childhood-onset asthma. Biomarker of lung squamous cell carcinoma and type 1 diabetes mellitus.

Source: NCBI Gene 124626 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 32 (top 4% of genes corpus-wide)
• Clinical variants (ClinVar): 36 total
• GTEx eGene: eQTL in 4 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.23 (unconstrained)
• MANE Select transcript: NM_199321

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20678
Approved symbol	ZPBP2
Name	zona pellucida binding protein 2
Location	17q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ZPBPL, MGC41930
Ensembl gene	ENSG00000186075
Ensembl biotype	protein_coding
OMIM	608499
Entrez	124626

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

MANE Select: ENST00000348931

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 5: 1

ENST00000348931, ENST00000377940, ENST00000583811, ENST00000584588, ENST00001094585, ENST00001130806

RefSeq mRNA: 2 — MANE Select: NM_199321 NM_198844, NM_199321

CCDS: CCDS11352, CCDS11353

Canonical transcript exons

ENST00000348931 — 8 exons

Exon	Start	End
ENSE00001332850	39875254	39875434
ENSE00001332851	39873044	39873126
ENSE00001332853	39872270	39872488
ENSE00001332854	39871464	39871625
ENSE00001332855	39870694	39870819
ENSE00001332856	39876682	39877896
ENSE00001377163	39868549	39868614
ENSE00002706078	39868202	39868406

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 98.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3052 / max 293.6563, expressed in 9 samples.

Highest expression (Bgee): sperm, testis, adult organism, male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ZPBP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	6.7e-28	-0.23	17:39876427:T:C
Testis	sqtl	9.5e-22	+0.72	17:39868373:C:T
Spleen	eqtl	4.4e-08	+0.48	17:39874911:T:C
Cells EBV-transformed lymphocytes	eqtl	3.1e-06	+0.42	17:39905964:C:T
Small Intestine Terminal Ileum	eqtl	4.4e-02	-0.79	17:39607530:G:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
160638	0.1990	6
160640	0.0969	5
160639	0.0093	4

Top tissues by expression

showing 100 of 195 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.99	gold quality
right testis	UBERON:0004534	96.30	gold quality
left testis	UBERON:0004533	96.26	gold quality
adult organism	UBERON:0007023	94.36	gold quality
testis	UBERON:0000473	93.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.99	gold quality
secondary oocyte	CL:0000655	73.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.29	gold quality
oocyte	CL:0000023	66.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
epithelial cell of pancreas	CL:0000083	53.74	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
pancreatic ductal cell	CL:0002079	52.54	silver quality
lymph node	UBERON:0000029	50.71	gold quality
myocardium	UBERON:0002349	50.25	gold quality
vermiform appendix	UBERON:0001154	49.49	gold quality
cerebellar vermis	UBERON:0004720	48.32	gold quality
caecum	UBERON:0001153	47.34	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
quadriceps femoris	UBERON:0001377	46.79	gold quality
tibialis anterior	UBERON:0001385	46.73	silver quality
deltoid	UBERON:0001476	46.37	gold quality
ileal mucosa	UBERON:0000331	46.10	silver quality
vastus lateralis	UBERON:0001379	45.40	gold quality
sural nerve	UBERON:0015488	45.39	gold quality
granulocyte	CL:0000094	45.14	silver quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
tonsil	UBERON:0002372	43.06	gold quality
muscle tissue	UBERON:0002385	42.33	gold quality
bone marrow	UBERON:0002371	42.13	gold quality
spleen	UBERON:0002106	41.97	silver quality
colonic epithelium	UBERON:0000397	41.84	gold quality
thymus	UBERON:0002370	41.58	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
endometrium	UBERON:0001295	41.29	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
monocyte	CL:0000576	40.77	gold quality
skeletal muscle tissue	UBERON:0001134	40.77	gold quality
cartilage tissue	UBERON:0002418	40.77	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
blood	UBERON:0000178	40.69	silver quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
metanephros	UBERON:0000081	40.20	silver quality
jejunum	UBERON:0002115	40.18	gold quality
epithelium of mammary gland	UBERON:0003244	40.14	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
colonic mucosa	UBERON:0000317	40.00	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
urethra	UBERON:0000057	39.80	gold quality
duodenum	UBERON:0002114	39.80	silver quality
heart right ventricle	UBERON:0002080	39.79	gold quality
pericardium	UBERON:0002407	39.77	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
dorsal root ganglion	UBERON:0000044	39.68	gold quality
nipple	UBERON:0002030	39.68	gold quality
bronchial epithelial cell	CL:0002328	39.65	gold quality
decidua	UBERON:0002450	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality
gingiva	UBERON:0001828	39.64	gold quality
bronchus	UBERON:0002185	39.64	gold quality
trigeminal ganglion	UBERON:0001675	39.63	gold quality
tendon of biceps brachii	UBERON:0008188	39.60	gold quality
inferior vagus X ganglion	UBERON:0005363	39.57	gold quality
superior surface of tongue	UBERON:0007371	39.56	gold quality
pylorus	UBERON:0001166	39.55	gold quality
nasal cavity mucosa	UBERON:0001826	39.54	gold quality
renal medulla	UBERON:0000362	39.53	gold quality
pons	UBERON:0000988	39.51	gold quality
medulla oblongata	UBERON:0001896	39.48	gold quality
superior vestibular nucleus	UBERON:0007227	39.47	gold quality
cardia of stomach	UBERON:0001162	39.46	gold quality
parietal pleura	UBERON:0002400	39.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	39.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	39.38	gold quality
tongue	UBERON:0001723	39.37	gold quality
oral cavity	UBERON:0000167	39.35	gold quality
subthalamic nucleus	UBERON:0001906	39.35	gold quality
ventral tegmental area	UBERON:0002691	39.35	gold quality
trachea	UBERON:0003126	39.33	gold quality
parietal lobe	UBERON:0001872	39.32	gold quality
vena cava	UBERON:0004087	39.31	gold quality
pharyngeal mucosa	UBERON:0000355	39.27	gold quality
substantia nigra pars compacta	UBERON:0001965	39.23	gold quality
visceral pleura	UBERON:0002401	39.23	gold quality
postcentral gyrus	UBERON:0002581	39.23	gold quality
body of tongue	UBERON:0011876	39.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	29.66
E-ANND-3	yes	3.26

HPA expression

RNA tissue specificity: Tissue enriched

37 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	89.1	high
Postcentral gyrus	tissue	4.7
Hippocampus	tissue	3.5	not detected
Nucleus accumbens	tissue	3.4
Locus coeruleus	tissue	3.2
Choroid plexus	tissue	3.1
Tonsil	tissue	0.8	not detected
Lymph node	tissue	0.6	not detected
Retina	tissue	0.5
Bone marrow	tissue	0.3	not detected
Appendix	tissue	0.3	not detected
Skeletal muscle	tissue	0.2	not detected
Spleen	tissue	0.2	not detected
Duodenum	tissue	0.2	not detected
Periaqueductal gray	tissue	0.2
Skin 1	tissue	0.1	not detected
Breast	tissue	0.1	not detected
Prefrontal cortex	tissue	0.1
Stomach 1	tissue	0.1	not detected
Cerebral cortex	tissue	0.1	not detected
Pons	tissue	0.1
Salivary gland	tissue	0.1	not detected
Rectum	tissue	0.1	not detected
Tongue	tissue	0.1
Midbrain	tissue	0.1
Medulla oblongata	tissue	0.1
Thalamus	tissue	0.1
Superior colliculi	tissue	0.1
Substantia nigra	tissue	0.1
Liver	tissue	0.1	not detected
Spinal cord	tissue	0.1
Corpus callosum	tissue	0.1
Prostate	tissue	0.1	not detected
Thymus	tissue	0.1
Hippocampal formation	tissue	0.1
Olfactory bulb	tissue	0.1
Temporal cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 186; highest nTPM — Somatosensory cortex, postcentral gyrus, ventral (white matter) (4.9), Flocculonodular lobe (4.8), Lingual gyrus (4.7), Posterior insular cortex (4.7), Parietal operculum (4.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ZPBP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 66 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514

Functional genomics

gnomAD constraint: pLI 2.47e-09, LOEUF 1.23, missense Z 0.46 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000348931 — one region, missense o/e 0.96.

Literature-anchored findings (GeneRIF, showing 9)

• Data show that loss of zona pellucida binding proteins 1 and 2 in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. (PMID:17664285)
• The disease-linked haplotype and putative causal DNA variants of ZPBP2/GSDMB/ORMDL3 locus via a combination of genetic and functional analyses, were identified. (PMID:19732864)
• allele-specific transcriptional regulation of genes in the asthma-associated chromosomal region 17q12-q21; rs4795397 influences activity of ZPBP2 promoter in an allele-dependent fashion and leads to nucleosome repositioning on the asthma-associated allele; methylation of exon 1 of ZPBP2 masks the genetic effect on ZPBP2 promoter; ORMDL3 promoter is unmethylated (PMID:22271045)
• Four additional susceptibility loci (IRF8, TMEM39A, IKZF3, and ZPBP2) for systemic lupus erythematosus were robustly established a multiethnic population (European, African American, Asian, Hispanic, Gullah, and Amerindian). (PMID:22464253)
• The allele T of rs10852936 surrounding the IKZF3-ZPBP2 locus confers risk for early-onset psoriasis. (PMID:25620289)
• The local genotype influences methylation levels at SLC22A5 and ZPBP2 promoters independently of the asthma status. Further studies are necessary to confirm the relationship between GSDMA-ZPBP2 and SLC22A5 methylation and asthma in females and males separately. (PMID:26671913)
• modest changes (8-13%) in promoter methylation levels of ZPBP2 and GSDMA may cause substantial changes in RNA levels and allelic expression of ZPBP2 and ORMDL3 is mediated by DNA methylation (PMID:28241063)
• Study of diurnal expression profiles of ZPBP2/Zpbp2, gasdermin B, and ORMDL3/Ormdl3 in human and mouse tissues revealed that Ormdl3 and Zpbp2 were controlled by the circadian clock in a tissue-specific fashion provided the first evidence that disease-associated genes Zpbp2 and Ormdl3 are regulated by circadian rhythms and the Zpbp2 region influences expression of the core clock gene Nr1d1. (PMID:31560728)
• The Germ Cell-Specific Markers ZPBP2 and PGK2 in Testicular Biopsies Can Predict the Presence as well as the Quality of Sperm in Non-obstructive Azoospermia Patients. (PMID:33507524)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zpbp2	ENSMUSG00000017195
rattus_norvegicus	Zpbp2	ENSRNOG00000007255

Paralogs (1): ZPBP (ENSG00000042813)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1916626) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
reduced male fertility	1
delayed fertilization	1
teratozoospermia	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	Q29108	82.9%	Diamond
Gallus gallus	Q6Q2W4	61.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ERBB2	protein-coding	2064
IKZF3	protein-coding	22806
GRB7	protein-coding	2886
MIEN1	protein-coding	84299
LRRC3C	protein-coding	100505591
GSDMB	protein-coding	55876
ORMDL3	protein-coding	94103
GSDMA	protein-coding	284110

Protein

Protein identifiers

Zona pellucida-binding protein 2 — Q6X784 (reviewed: Q6X784)

Alternative names: ZPBP-like protein

All UniProt accessions (3): J3KRM0, J3KSF6, Q6X784

UniProt curated annotations — full annotation on UniProt →

Function. Is implicated in sperm-oocyte interaction during fertilization.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Secreted.

Tissue specificity. Expressed specifically in testis.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the zona pellucida-binding protein Sp38 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6X784-1	1	yes
Q6X784-2	2

RefSeq proteins (2): NP_942141, NP_955353* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007110	Ig-like_dom	Domain
IPR010857	Sp38-bd	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR048805	ZPBP1/2_C	Domain
IPR048806	ZPBP1/2_N	Domain

Pfam: PF07354, PF20626

UniProt features (12 total): sequence variant 5, glycosylation site 4, signal peptide 1, chain 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6X784-F1	86.81	0.70

Human Protein Atlas

Protein class: Predicted secreted proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

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

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	87, 221, 257, 309

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 131 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_SINGLE_FERTILIZATION, AP1_01, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GOBP_MALE_GAMETE_GENERATION, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, COUP_01, GOBP_REGULATION_OF_IMMUNOGLOBULIN_PRODUCTION, AP1_Q4_01, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS

GO Biological Process (2): acrosome assembly (GO:0001675), binding of sperm to zona pellucida (GO:0007339)

GO Cellular Component (6): acrosomal vesicle (GO:0001669), zona pellucida receptor complex (GO:0002199), extracellular region (GO:0005576), nucleus (GO:0005634), cell body (GO:0044297), cytoplasmic vesicle (GO:0031410)

GO top-level categories

14 GO namespaces:

Category	Terms
cellular anatomical structure	2
developmental process involved in reproduction	1
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
sperm-egg recognition	1
secretory granule	1
chaperonin-containing T-complex	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 8 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
nucleus	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 994 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZPBP2	GSDMB	Q8TAX9	941
ZPBP2	IKZF3	Q9UKT9	923
ZPBP2	ORMDL3	Q8N138	922
ZPBP2	GRB7	Q14451	752
ZPBP2	LRRC3C	A6NJW4	741
ZPBP2	GSDMA	Q96QA5	602
ZPBP2	ACRBP	Q8NEB7	595
ZPBP2	IKZF1	Q13422	583
ZPBP2	CTCF	P49711	583
ZPBP2	PGAP3	Q96FM1	570
ZPBP2	GRB10	Q13322	561
ZPBP2	SPACA3	Q8IXA5	469
ZPBP2	SPACA1	Q9HBV2	467
ZPBP2	MAN2B2	Q9Y2E5	442
ZPBP2	C10orf120	Q5SQS8	441

IntAct

Human interaction partners of ZPBP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
CD80	physical association	0.400	1
PALM	association	0.350	1
PPP1R1A	association	0.350	1

BioGRID (32 interactions; top human partners by supporting records): NPTX1 (Affinity Capture-MS; 3 records), PPP1R1A (Affinity Capture-MS; 3 records), PROS1 (Affinity Capture-MS; 3 records), TUBB8 (Affinity Capture-MS; 3 records), ZNF146 (Affinity Capture-MS; 3 records), OS9 (Affinity Capture-MS; 2 records), SEL1L (Affinity Capture-MS; 2 records), CRELD2 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), IL17RA (Affinity Capture-MS), LRP11 (Affinity Capture-MS), MSLN (Affinity Capture-MS), NOMO1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for ZPBP2: 36 ClinVar records (0 pathogenic / likely pathogenic); 32 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 974):

Position(s)	Effect	Δscore	Sites
17:39871462–39871463	acceptor_loss	1.0000	6
17:39871606	donor_gain	1.0000
17:39871626–39871627	donor_loss	1.0000	5
17:39875247	acceptor_gain	1.0000
17:39875252–39875253	acceptor_loss	1.0000	4
17:39870692–39870693	acceptor_loss	0.9900	6
17:39870820–39870821	donor_loss	0.9900	5
17:39871560	acceptor_gain	0.9900
17:39871627	donor_loss	0.9900
17:39872267–39872268	acceptor_gain	0.9900	2

AlphaMissense

459 missense substitutions predicted likely pathogenic (of 2,244 scored), across 119 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F207	8	0.887	0.973
F245	8	0.798	0.890
F282	7	0.948	0.989
W72	7	0.935	0.982
C299	7	0.929	0.955
C109	7	0.925	0.954
C278	7	0.920	0.948
C55	7	0.912	0.944
F150	7	0.900	0.969
C189	7	0.889	0.944
C312	7	0.883	0.921
C296	7	0.881	0.923
F99	7	0.856	0.961
C180	7	0.848	0.929
F204	7	0.847	0.957
C292	7	0.832	0.891
F265	7	0.827	0.936
C155	7	0.813	0.856
F212	7	0.811	0.937
C295	7	0.793	0.837

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:608499 | disease phenotypes:

GWAS associations

showing 30 of 32 associations:

Study	Trait	p-value
GCST007995_2	Asthma (childhood onset)	1e-111
GCST009798_36	Asthma	1e-65
GCST007994_15	Asthma (age of onset)	7e-65
GCST003987_3	Asthma	1e-63
GCST008916_121	Asthma	2e-62
GCST001725_54	Inflammatory bowel disease	4e-38
GCST005537_6	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	6e-30
GCST004131_33	Inflammatory bowel disease	2e-26
GCST005213_5	Asthma (childhood onset)	4e-26
GCST010002_175	Refractive error	1e-24
GCST006409_8	Allergic rhinitis	2e-17
GCST007564_34	Asthma or allergic disease (pleiotropy)	4e-17
GCST004132_53	Crohn’s disease	1e-16
GCST004133_68	Ulcerative colitis	2e-16
GCST008838_5	Asthma (time to onset)	2e-16
GCST005581_40	Primary biliary cirrhosis	6e-14
GCST004390_1	Asthma	4e-12
GCST007036_1	Primary biliary cholangitis	4e-12
GCST007266_5	Adult asthma	4e-12
GCST006414_135	Atrial fibrillation	3e-11
GCST000964_26	Ulcerative colitis	5e-11
GCST000733_2	Primary biliary cholangitis	2e-9
GCST000879_10	Crohn’s disease	2e-9
GCST001685_2	Primary biliary cholangitis	4e-9
GCST002304_21	Fractional exhaled nitric oxide (childhood)	2e-8
GCST006940_106	Neurociticism	2e-8
GCST000624_15	Ulcerative colitis	3e-8
GCST006537_1	Subcutaneous adipose tissue	3e-8
GCST009877_22	Rheumatoid arthritis	6e-7
GCST006061_1	Atrial fibrillation	3e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0005536	nitric oxide exhalation measurement
EFO:0007660	neuroticism measurement
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
MT19c compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Folic Acid	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.