DZIP1

Summary

DZIP1 (DAZ interacting zinc finger protein 1, HGNC:20908) is a protein-coding gene on chromosome 13q32.1, encoding Cilium assembly protein DZIP1 (Q86YF9). Molecular adapter that recruits protein complexes required for cilium assembly and function to the cilium basal body.

Enables BBSome binding activity and molecular adaptor activity. Involved in cilium organization; heart development; and protein-containing complex localization to centriolar satellite. Located in cytosol; microtubule organizing center; and nucleoplasm. Implicated in mitral valve prolapse and spermatogenic failure 47.

Source: NCBI Gene 22873 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitral valve prolapse (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 142 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_198968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20908
Approved symbol	DZIP1
Name	DAZ interacting zinc finger protein 1
Location	13q32.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0996, DZIP
Ensembl gene	ENSG00000134874
Ensembl biotype	protein_coding
OMIM	608671
Entrez	22873

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 21 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000347108, ENST00000361156, ENST00000361396, ENST00000376829, ENST00000466027, ENST00000466569, ENST00000479518, ENST00000485031, ENST00000897703, ENST00000897704, ENST00000897705, ENST00000897706, ENST00000897707, ENST00000897708, ENST00000897709, ENST00000897710, ENST00000897711, ENST00000897712, ENST00000926436, ENST00000926437, ENST00000926438, ENST00000926439, ENST00000947291, ENST00000947292, ENST00000947293

RefSeq mRNA: 2 — MANE Select: NM_198968 NM_014934, NM_198968

CCDS: CCDS9477, CCDS9478

Canonical transcript exons

ENST00000376829 — 23 exons

Exon	Start	End
ENSE00001144694	95643601	95643698
ENSE00001471826	95578202	95582313
ENSE00001471828	95643043	95643257
ENSE00001529561	95644377	95644706
ENSE00001677710	95589803	95589932
ENSE00001687967	95590279	95590441
ENSE00001703634	95589154	95589207
ENSE00001720192	95593944	95594086
ENSE00001766225	95599365	95599424
ENSE00001788316	95587539	95587729
ENSE00002308916	95633234	95633321
ENSE00003459333	95584736	95584910
ENSE00003521166	95609457	95609513
ENSE00003525983	95586006	95586136
ENSE00003568788	95612037	95612177
ENSE00003591289	95629989	95630113
ENSE00003597039	95624768	95624929
ENSE00003627893	95619885	95619947
ENSE00003632175	95606003	95606059
ENSE00003635983	95641994	95642241
ENSE00003651420	95641295	95641855
ENSE00003659723	95622343	95622480
ENSE00003684851	95611445	95611493

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4893 / max 83.4507, expressed in 1141 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137894	3.2665	1103
137893	0.7558	385
137892	0.3054	181
137890	0.0501	10
137891	0.0306	6
137883	0.0196	4
137882	0.0119	4
137889	0.0109	4
137885	0.0093	3
137881	0.0083	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.84	gold quality
male germ cell	CL:0000015	97.95	gold quality
left testis	UBERON:0004533	94.96	gold quality
calcaneal tendon	UBERON:0003701	94.56	gold quality
right testis	UBERON:0004534	94.41	gold quality
testis	UBERON:0000473	93.99	gold quality
ventricular zone	UBERON:0003053	93.89	gold quality
caput epididymis	UBERON:0004358	92.21	gold quality
right frontal lobe	UBERON:0002810	92.17	gold quality
secondary oocyte	CL:0000655	92.13	gold quality
stromal cell of endometrium	CL:0002255	92.06	gold quality
tendon	UBERON:0000043	91.96	gold quality
cerebellar hemisphere	UBERON:0002245	91.95	gold quality
nucleus accumbens	UBERON:0001882	91.90	gold quality
cingulate cortex	UBERON:0003027	91.83	gold quality
amygdala	UBERON:0001876	91.81	gold quality
cerebellar cortex	UBERON:0002129	91.73	gold quality
anterior cingulate cortex	UBERON:0009835	91.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.51	gold quality
tendon of biceps brachii	UBERON:0008188	91.47	gold quality
left ovary	UBERON:0002119	91.31	gold quality
oocyte	CL:0000023	90.95	gold quality
hypothalamus	UBERON:0001898	90.89	gold quality
right ovary	UBERON:0002118	90.71	gold quality
adenohypophysis	UBERON:0002196	90.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.56	gold quality
cerebellum	UBERON:0002037	90.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.22	gold quality
ovary	UBERON:0000992	89.89	gold quality
caudate nucleus	UBERON:0001873	89.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

139 targeting DZIP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290

Literature-anchored findings (GeneRIF, showing 8)

• DZIP may associate with DAZ and its other cofactors in an RNA-binding protein complex that functions in both ES cells and germ cells (PMID:15081113)
• gene expression profiling [DZIP] (PMID:15081113)
• reversible phosphorylation of Dzip1, which is controlled by the antagonistic action of CK2 and B56-containing PP2As, has an important impact on the stability of Gli transcription factors and Hh signaling. (PMID:21878643)
• Dzip1-dependent stabilization of Spop/HIB is evolutionarily conserved and essential for proper regulation of Gli/Ci proteins in the Hh pathway. (PMID:24072710)
• The abundance of DZIP1-associated mRNAs increased with treatment. (PMID:24993635)
• centrosome protein Dzip1 mediates the assembly of the BBSome-Dzip1-PCM1 complex in the centriolar satellites (CS) at the G0 phase for ciliary translocation of the BBSome. Phosphorylation of Dzip1 at Ser-210 by Plk1 (polo-like kinase 1) during the G2 phase promotes disassembly of this complex, resulting in removal of Dzip1 and the BBSome from the CS. (PMID:27979967)
• In conclusion, we identified two genes, DZIP1 and XYLT1, potentially associated with nonsyndromic high myopia using whole exome sequencing and subsequent mutation screening analysis. (PMID:28085539)
• Homozygous mutations in DZIP1 can induce asthenoteratospermia with severe MMAF. (PMID:32051257)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dzip1	ENSDARG00000000943
mus_musculus	Dzip1	ENSMUSG00000042156
rattus_norvegicus	Dzip1	ENSRNOG00000010311
rattus_norvegicus	Dzip1-ps1	ENSRNOG00000046611

Paralogs (4): RILPL2 (ENSG00000150977), DZIP1L (ENSG00000158163), RILP (ENSG00000167705), RILPL1 (ENSG00000188026)

Protein

Protein identifiers

Cilium assembly protein DZIP1 — Q86YF9 (reviewed: Q86YF9)

Alternative names: DAZ-interacting protein 1/2, DAZ-interacting zinc finger protein 1

All UniProt accessions (1): Q86YF9

UniProt curated annotations — full annotation on UniProt →

Function. Molecular adapter that recruits protein complexes required for cilium assembly and function to the cilium basal body. At the exit of mitosis, localizes to the basal body and ciliary base of the forming primary cilium where it recruits and activates RAB8A to direct vesicle-mediated transport of proteins to the cilium. Also recruits the BBSome, a complex involved in cilium biogenesis, by bridging it to PCM1 at the centriolar satellites of the cilium. It is also required for the recruitment to the cilium basal body of the intraflagellar transport (IFT) machinery as well as the ciliary appendage proteins CEP164 and NINEIN. Functions as a regulator of Hedgehog signaling both through its role in cilium assembly but also probably through its ability to retain GLI3 within the cytoplasm. It is involved in spermatogenesis through its role in organization of the basal body and assembly of the sperm flagellum. Also indirectly involved in heart development through its function in ciliogenesis.

Subunit / interactions. Interacts with DAZ1. Interacts with the BBSome; recruits the BBSome to centriolar satellites of the cilium. Interacts with PCM1; localizes DZIP1 and the associated BBSome to centriolar satellites. Interacts with RAB8A (GDP-bound inactive form); recruits RAB8A to the basal body of the cilium and prevents its inhibition by GDI2. Interacts with GDI2; negatively regulates the interaction of GDI2 with GDP-bound RAB8A. Interacts with GLI3; retains GLI3 within the cytoplasm. Interacts with CEP164. Interacts with IFT88.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body. Microtubule organizing center. Centrosome. Centriolar satellite. Centriole. Nucleus. Nucleus speckle.

Tissue specificity. Predominantly expressed in testis (at protein level). Also expressed in fetal brain, adult oocytes and ovary. Expressed in undifferentiated ES cells. In testis, it is specifically expressed in germ cells (at protein level). Expressed in mature germ cells and secondary spermatocytes, while it is weakly or not expressed in primary spermatocytes.

Post-translational modifications. Phosphorylation at Ser-226 by PLK1 before mitosis prevents interaction with PCM1 and localization to centriolar satellites. Thereby, it negatively regulates the localization of the BBSome to centriolar satellites.

Disease relevance. Mitral valve prolapse 3 (MVP3) [MIM:610840] An autosomal dominant form of mitral valve prolapse, a valvular heart disease characterized by abnormally elongated and thickened mitral valve leaflets, that typically show myxomatous degeneration with increased leaflet compliance. It is associated with mitral regurgitation. Myxomatous mitral valves have an abnormal layered architecture characterized by loose collagen in fibrosa, expanded spongiosa strongly positive for proteoglycans, and disrupted elastin in atrialis. In classic mitral valve prolapse, leaflets are at least 5 mm thick, whereas in the non-classic form, they are less than 5 mm thick. Severe classic mitral valve prolapse is strongly associated with arrhythmias, endocarditis, heart failure, and need for valve surgery. The disease is caused by variants affecting the gene represented in this entry. Spermatogenic failure 47 (SPGF47) [MIM:619102] An autosomal recessive infertility disorder caused by spermatogenesis defects resulting in asthenoteratozoospermia. SPGF47 is characterized by reduced sperm concentrations and immotile spermatozoa, with short or absent flagella as well as centriolar abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the DZIP C2H2-type zinc-finger protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86YF9-1	1, DZIPt2, DZIP testis2	yes
Q86YF9-2	2, DZIPt1, DZIP testis1
Q86YF9-3	3, DZIPb, DZIP brain

RefSeq proteins (2): NP_055749, NP_945319* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR032714	DZIP1_N	Domain
IPR051241	DZIP_RILPL	Family
IPR058883	DZIP1_dom	Domain

Pfam: PF13815, PF25977

UniProt features (30 total): compositionally biased region 6, region of interest 6, sequence variant 6, splice variant 4, coiled-coil region 3, sequence conflict 2, chain 1, zinc finger region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YF9-F1	65.55	0.27

Functional residue map

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

Post-translational modifications (1): 226

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5632684	Hedgehog ‘on’ state

MSigDB gene sets: 269 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, YY1_Q6, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, MORF_ZNF10, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, MODULE_205, YY1_02, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOCC_CENTROSOME

GO Biological Process (16): smoothened signaling pathway (GO:0007224), germ cell development (GO:0007281), spermatogenesis (GO:0007283), heart development (GO:0007507), ciliary basal body organization (GO:0032053), establishment of protein localization (GO:0045184), positive regulation of cilium assembly (GO:0045724), establishment of localization in cell (GO:0051649), cilium assembly (GO:0060271), protein localization to cilium (GO:0061512), sperm flagellum assembly (GO:0120316), protein-containing complex localization to centriolar satellite (GO:0140706), positive regulation of protein localization to cilium (GO:1903566), cell projection organization (GO:0030030), cell differentiation (GO:0030154), cilium organization (GO:0044782)

GO Molecular Function (6): zinc ion binding (GO:0008270), molecular adaptor activity (GO:0060090), BBSome binding (GO:0062063), protein sequestering activity (GO:0140311), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), nuclear speck (GO:0016607), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), ciliary transition fiber (GO:0097539), ciliary base (GO:0097546), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Hedgehog	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
developmental process involved in reproduction	3
microtubule organizing center	3
cilium	3
cilium organization	2
establishment of localization	2
protein localization to cilium	2
binding	2
intracellular membraneless organelle	2
cell surface receptor signaling pathway	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
male gamete generation	1
animal organ development	1
circulatory system development	1
microtubule organizing center organization	1
cilium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
cellular localization	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
protein localization to organelle	1
spermatid development	1
flagellated sperm motility	1
motile cilium assembly	1
protein-containing complex localization	1
regulation of protein localization to cilium	1
positive regulation of protein localization	1
cellular component organization	1
cellular developmental process	1
organelle organization	1
plasma membrane bounded cell projection organization	1
transition metal ion binding	1

Protein interactions and networks

STRING

1283 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DZIP1	DAZ1	Q9NQZ3	929
DZIP1	DAZL	Q92904	801
DZIP1	HMMR	O75330	767
DZIP1	TTC29	Q8NA56	587
DZIP1	RAB8A	P24407	576
DZIP1	CFAP69	A5D8W1	562
DZIP1	TTC21A	Q8NDW8	554
DZIP1	DZIP3	Q86Y13	531
DZIP1	CIBAR1	A1XBS5	528
DZIP1	QRICH2	Q9H0J4	520
DZIP1	CFAP70	Q5T0N1	512
DZIP1	FSIP2	Q5CZC0	503
DZIP1	CFAP43	Q8NDM7	493
DZIP1	CFAP251	Q8TBY9	493
DZIP1	CFAP44	Q96MT7	491

IntAct

53 interactions, top by confidence:

A	B	Type	Score
PPP2R5A	DZIP1	psi-mi:“MI:0915”(physical association)	0.670
DZIP1	PPP2R5E	psi-mi:“MI:0915”(physical association)	0.580
PPP2R5E	DZIP1	psi-mi:“MI:0915”(physical association)	0.580
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
PRPF40A	DZIP1	psi-mi:“MI:0915”(physical association)	0.560
DZIP1	LUC7L2	psi-mi:“MI:0915”(physical association)	0.560
PPP1R18	DZIP1	psi-mi:“MI:0915”(physical association)	0.560
MOS	DZIP1	psi-mi:“MI:0915”(physical association)	0.560
TNS2	DZIP1	psi-mi:“MI:0915”(physical association)	0.560
GSK3B	DZIP1	psi-mi:“MI:0915”(physical association)	0.400
DZIP1	HMGB2	psi-mi:“MI:0915”(physical association)	0.400
DZIP1	UTP3	psi-mi:“MI:0915”(physical association)	0.400
PPP2R5D	DZIP1	psi-mi:“MI:0915”(physical association)	0.370
DZIP1	PPP2R5B	psi-mi:“MI:0915”(physical association)	0.370
PPP2R5C	DZIP1	psi-mi:“MI:0915”(physical association)	0.370
DAZ1	DZIP1	psi-mi:“MI:0915”(physical association)	0.370
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
CAMK2G	PSMD12	psi-mi:“MI:0914”(association)	0.350
CAMK2A	OGT	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MCC	CIBAR1	psi-mi:“MI:0914”(association)	0.350
PER2	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CBY1	RHOA	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
FAM9B	CIBAR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): DZIP1 (Synthetic Growth Defect), DZIP1 (Affinity Capture-RNA), DZIP1 (Two-hybrid), DZIP1 (Two-hybrid), PPP1R18 (Two-hybrid), LUC7L2 (Two-hybrid), MOS (Two-hybrid), PRPF40A (Two-hybrid), UTP3 (Proximity Label-MS), DZIP1 (Proximity Label-MS), DZIP1 (Two-hybrid), DZIP1 (Affinity Capture-RNA), DZIP1 (Proximity Label-MS), DZIP1 (Proximity Label-MS), DZIP1 (Proximity Label-MS)

ESM2 similar proteins: A0JMQ7, A0JP75, A1A600, A2BGP7, B1A193, B1WBU8, B2RPU2, G9G127, H2MTR9, O88869, Q0VFN8, Q2TAA8, Q32LC2, Q3ULW6, Q3UP38, Q4R7V1, Q4V7B0, Q5EB20, Q5JU67, Q5PQQ9, Q5RDE3, Q5U4W1, Q5XIR4, Q61043, Q6AXZ4, Q6IP02, Q6IQY5, Q6IRU7, Q6NRK1, Q6NRX3, Q6PA69, Q6ZQ12, Q7Z3E5, Q86YF9, Q86YS3, Q8BIJ7, Q8BQP8, Q8CGZ2, Q8CJ96, Q8K342

Diamond homologs: Q32PN7, Q499E4, Q5XIA0, Q7T019, Q86YF9, Q8BMD2, Q8IYY4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GSK3B	“up-regulates activity”	DZIP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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
Signaling by GSK3beta mutants	6	138.4×	7e-11
CTNNB1 S33 mutants aren’t phosphorylated	6	138.4×	7e-11
CTNNB1 S37 mutants aren’t phosphorylated	6	138.4×	7e-11
CTNNB1 S45 mutants aren’t phosphorylated	6	138.4×	7e-11
CTNNB1 T41 mutants aren’t phosphorylated	6	138.4×	7e-11
Beta-catenin phosphorylation cascade	6	122.1×	2e-10
Activation of BAD and translocation to mitochondria	5	115.3×	7e-09
Platelet sensitization by LDL	5	101.8×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	6	15.3×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	115
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
984962	NM_198968.4(DZIP1):c.690T>G (p.Tyr230Ter)	Pathogenic
984963	NM_198968.4(DZIP1):c.188G>A (p.Arg63Gln)	Pathogenic
4845739	NM_198968.4(DZIP1):c.2248dup (p.Val750fs)	Likely pathogenic
4849321	NM_198968.4(DZIP1):c.1107_1110del (p.Ser369fs)	Likely pathogenic

SpliceAI

3656 predictions. Top by Δscore:

Variant	Effect	Δscore
13:95584741:C:CA	donor_gain	1.0000
13:95584822:T:TA	donor_gain	1.0000
13:95584835:T:A	donor_gain	1.0000
13:95584864:T:TA	donor_gain	1.0000
13:95584907:CACA:C	acceptor_gain	1.0000
13:95584908:ACA:A	acceptor_gain	1.0000
13:95584908:ACAC:A	acceptor_loss	1.0000
13:95584909:CA:C	acceptor_gain	1.0000
13:95584909:CAC:C	acceptor_gain	1.0000
13:95584909:CACTA:C	acceptor_loss	1.0000
13:95584910:ACTAA:A	acceptor_loss	1.0000
13:95584911:C:CC	acceptor_gain	1.0000
13:95584911:C:T	acceptor_loss	1.0000
13:95584912:T:C	acceptor_loss	1.0000
13:95586000:TTTCA:T	donor_loss	1.0000
13:95586001:TTCAC:T	donor_loss	1.0000
13:95586002:TCACC:T	donor_loss	1.0000
13:95586003:CACCT:C	donor_loss	1.0000
13:95586004:A:T	donor_loss	1.0000
13:95586025:T:TA	donor_gain	1.0000
13:95586132:GACTC:G	acceptor_gain	1.0000
13:95586133:ACTC:A	acceptor_gain	1.0000
13:95586134:CTC:C	acceptor_gain	1.0000
13:95586134:CTCC:C	acceptor_gain	1.0000
13:95586135:TC:T	acceptor_gain	1.0000
13:95586135:TCC:T	acceptor_loss	1.0000
13:95586135:TCCT:T	acceptor_gain	1.0000
13:95586136:CC:C	acceptor_gain	1.0000
13:95586137:C:CC	acceptor_gain	1.0000
13:95586146:CAA:C	acceptor_gain	1.0000

AlphaMissense

5783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:95633298:A:C	F207L	1.000
13:95633298:A:T	F207L	1.000
13:95633300:A:G	F207L	1.000
13:95633260:C:G	R220P	0.999
13:95633261:G:T	R220S	0.999
13:95633263:C:G	R219P	0.999
13:95633264:G:T	R219S	0.999
13:95633271:G:C	H216Q	0.999
13:95633271:G:T	H216Q	0.999
13:95633273:G:C	H216D	0.999
13:95633281:A:G	L213P	0.999
13:95633299:A:C	F207C	0.999
13:95633299:A:G	F207S	0.999
13:95633304:C:A	K205N	0.999
13:95633304:C:G	K205N	0.999
13:95633311:C:T	C203Y	0.999
13:95633321:A:G	C200R	0.999
13:95641353:C:G	R180P	0.999
13:95641504:A:C	Y130D	0.999
13:95641522:C:G	A124P	0.999
13:95641524:A:G	L123P	0.999
13:95641533:A:G	L120P	0.999
13:95641576:A:G	C106R	0.999
13:95641598:G:C	F98L	0.999
13:95641598:G:T	F98L	0.999
13:95641600:A:G	F98L	0.999
13:95641626:A:G	L89P	0.999
13:95641626:A:T	L89Q	0.999
13:95641685:C:A	W69C	0.999
13:95641685:C:G	W69C	0.999

dbSNP variants (sampled 300 via entrez): RS1000063797 (13:95605098 T>G), RS1000157805 (13:95613624 A>T), RS1000233458 (13:95607606 G>T), RS1000233710 (13:95639710 TGTATGTTAGAG>T), RS1000281230 (13:95594644 A>G), RS1000282209 (13:95629135 T>TG), RS1000307655 (13:95585012 G>A), RS1000339825 (13:95642610 G>A,T), RS1000390939 (13:95622960 G>T), RS1000472234 (13:95618392 T>C), RS1000485522 (13:95624983 A>C), RS1000500736 (13:95607940 A>T), RS1000601216 (13:95624598 C>T), RS1000640021 (13:95583555 TA>T,TAA), RS1000679640 (13:95589645 G>A)

Disease associations

OMIM: gene MIM:608671 | disease phenotypes: MIM:618009, MIM:619102, MIM:610840

GenCC curated gene-disease

Disease	Classification	Inheritance
mitral valve prolapse	Moderate	Autosomal dominant
spermatogenic failure	Moderate	Autosomal recessive
spermatogenic failure 47	Limited	Autosomal recessive

Mondo (5): intellectual developmental disorder 61 (MONDO:0032485), spermatogenic failure 47 (MONDO:0030844), mitral valve prolapse, myxomatous 3 (MONDO:0012569), mitral valve prolapse (MONDO:0004910), spermatogenic failure (MONDO:0004983)

Orphanet (0):

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0001634	Mitral valve prolapse
HP:0001653	Mitral regurgitation
HP:0003251	Male infertility
HP:0003831	Typified by age-related disease onset
HP:0012208	Immotile sperm
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002675_4	Response to statins (LDL cholesterol change)	8.000000e-07
GCST003375_1	Glomerular filtration rate (cystatin C)	6.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004617	cystatin C measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008945	Mitral Valve Prolapse	C14.280.484.400.500
C563655	Mitral Valve Prolapse, Myxomatous 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	3
bisphenol A	increases expression, decreases methylation	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Nickel	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
terbufos	increases methylation	1
nickel chloride	decreases expression	1
hydroquinone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression	1
Cyclophosphamide	increases expression	1
Doxorubicin	affects response to substance	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Topotecan	affects response to substance	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05631730	PHASE3	RECRUITING	Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse
NCT01500148	PHASE1	COMPLETED	St. Jude Medical Percutaneous Mitral Valve Repair Study
NCT04299334	PHASE1	UNKNOWN	Neochordae Technique in Mitral Valve Repair
NCT00665301	Not specified	COMPLETED	Cardiac Output Pulmonary Arterial Catheter Compared to FloWave™ 1000
NCT00799565	Not specified	COMPLETED	Mitral Valve Prolapse (MVP) - France Study
NCT01719211	Not specified	UNKNOWN	Genetic Basis of Mitral Valve Prolapse
NCT02105480	Not specified	COMPLETED	Automated Algorithm Based Analysis of Phonocardiograms of Newborns
NCT02432196	Not specified	COMPLETED	CE Mark Study for the Harpoon Medical Device in Poland
NCT02499419	Not specified	UNKNOWN	Exercise Capacity Evaluation in Patients With Non-rheumatic Mitral Valve Prolapse (MVP)
NCT02512341	Not specified	COMPLETED	Automatic Differentiation of Innocent and Pathologic Murmurs in Pediatrics
NCT02552771	Not specified	UNKNOWN	The Canadian Mitral Research Alliance (CAMRA) Trial CardioLink-2
NCT02768870	Not specified	COMPLETED	CE Mark Study for the Harpoon Medical Device
NCT02771275	Not specified	COMPLETED	Safety and Early Feasibility Study of the Harpoon Medical Device (EFS)
NCT02879825	Not specified	COMPLETED	Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse (STAMP: STretch and Myocardial Characterization in Arrhythmogenic Mitral Valve Prolapse)
NCT03113552	Not specified	RECRUITING	Prognostic Impact of the Location of Mitral Valve Prolapse on the Long-term Results of Mitral Plasty
NCT03285724	Not specified	TERMINATED	Safety and Performance Study of the Harpoon Mitral Valve Repair System
NCT03470155	Not specified	COMPLETED	Operative Mitral Valve Reconstruction in Functional mv Insufficiency With Reduced Systolic Ventricle Function
NCT03506217	Not specified	UNKNOWN	Using Pulse Counter Vigileo-Flotrac System in Transapical Off-pump Minimally Invasive Mitral Valve Repair
NCT03609931	Not specified	UNKNOWN	Patient Specific Mitral Valve Modeling for Surgical Planning and Training
NCT03884426	Not specified	UNKNOWN	Genetic and Phenotypic Characteristics of Mitral Valve Prolapse
NCT04067635	Not specified	UNKNOWN	Primary Mitral Regurgitation Repair
NCT04190602	Not specified	RECRUITING	Multicenter Post-Market Observational Registry of the NeoChord Artificial Chordae Delivery System
NCT04231903	Not specified	COMPLETED	Myocardial Protection in Minimally Invasive Mitral Valve Surgery
NCT04770961	Not specified	UNKNOWN	Erector Spinae Plane Block for Minimally Invasive Mitral Valve Surgery
NCT04852731	Not specified	RECRUITING	STretch and Myocardial Characterization in Arrythmogenic Mitral Valve Prolapse-2
NCT05425628	Not specified	UNKNOWN	European FIH Study - NeoChord Transcatheter Mitral Repair System for Symptomatic Mitral Regurgitation
NCT05562804	Not specified	UNKNOWN	Mitral Valve Prolapse, Arrhythmias and Mitral Valve Surgery
NCT06255457	Not specified	RECRUITING	Ventricular Arrhythmias in Patients Undergoing Mitral Valve Surgery
NCT06341166	Not specified	RECRUITING	Multiparametric SCores for Prediction of Myocardial fIbrosis in Patients With MITral vAlve pRolapse
NCT06378996	Not specified	RECRUITING	Arrhythmic Mitral Valve Prolapse Detection Using Long-term Ambulatory Rhythm Monitoring
NCT06436573	Not specified	COMPLETED	Mitro-annular Disjunction in Cardiac Magnetic Resonance
NCT06738537	Not specified	RECRUITING	Patient-Centered Approach for Treatment Decisions in Mitral Valve Prolapse
NCT06741709	Not specified	NOT_YET_RECRUITING	A Study of Mitral Annular Disjunction in Mitral Valve Prolapse Patients and Arrhythmia Risk
NCT07068633	Not specified	NOT_YET_RECRUITING	Korea VHD Echo Study: Surveillance of Aortic, Mitral & Tricuspid Patients - Insights From Real-world Practice
NCT07103733	Not specified	RECRUITING	PRIMARY Ancillary Substudy
NCT07366723	Not specified	ACTIVE_NOT_RECRUITING	The Role of cardIac magNeTic rEsonance in surGical Decision Making in Patients With Severe pRimAry miTral rEgurgitation
NCT07384871	Not specified	RECRUITING	AI-Based Shape and Function Analysis of Mitral Valve Prolapse Using 3D Ultrasound