DYNC2I2

Summary

DYNC2I2 (dynein 2 intermediate chain 2, HGNC:28296) is a protein-coding gene on chromosome 9q34.11, encoding Cytoplasmic dynein 2 intermediate chain 2 (Q96EX3). Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system.

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Defects in this gene are a cause of short-rib thoracic dysplasia 11 with or without polydactyly.

Source: NCBI Gene 89891 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short-rib thoracic dysplasia 11 with or without polydactyly (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 598 total — 35 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 77
• MANE Select transcript: NM_052844

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28296
Approved symbol	DYNC2I2
Name	dynein 2 intermediate chain 2
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	DIC5, MGC20486, bA216B9.3, FAP133, CFAP133
Ensembl gene	ENSG00000119333
Ensembl biotype	protein_coding
OMIM	613363
Entrez	89891

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000372715, ENST00000419989, ENST00000451652, ENST00000473486, ENST00000480613, ENST00000483181, ENST00000854292, ENST00000854293, ENST00000925010, ENST00000925011, ENST00000946364, ENST00000946365

RefSeq mRNA: 1 — MANE Select: NM_052844 NM_052844

CCDS: CCDS6906

Canonical transcript exons

ENST00000372715 — 9 exons

Exon	Start	End
ENSE00000807000	128636918	128637027
ENSE00001458450	128656541	128656847
ENSE00001610590	128634226	128634383
ENSE00001685071	128633653	128633982
ENSE00001700666	128634689	128634921
ENSE00003513930	128635092	128635259
ENSE00003536703	128640691	128640939
ENSE00003604588	128635658	128635767
ENSE00003613548	128636281	128636438

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 97.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.9992 / max 266.9733, expressed in 1746 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102696	37.9992	1746

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.58	gold quality
pancreatic ductal cell	CL:0002079	96.86	gold quality
apex of heart	UBERON:0002098	96.33	gold quality
right lobe of thyroid gland	UBERON:0001119	95.99	gold quality
kidney epithelium	UBERON:0004819	95.99	gold quality
metanephros cortex	UBERON:0010533	95.66	gold quality
ventricular zone	UBERON:0003053	95.56	gold quality
right testis	UBERON:0004534	95.49	gold quality
left lobe of thyroid gland	UBERON:0001120	95.45	gold quality
left testis	UBERON:0004533	95.37	gold quality
mucosa of transverse colon	UBERON:0004991	95.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.27	gold quality
thyroid gland	UBERON:0002046	94.66	gold quality
bronchial epithelial cell	CL:0002328	94.39	gold quality
right adrenal gland	UBERON:0001233	94.03	gold quality
bronchus	UBERON:0002185	94.00	gold quality
left adrenal gland cortex	UBERON:0035825	93.98	gold quality
left adrenal gland	UBERON:0001234	93.94	gold quality
tendon of biceps brachii	UBERON:0008188	93.61	gold quality
testis	UBERON:0000473	93.50	gold quality
adrenal cortex	UBERON:0001235	93.37	gold quality
right adrenal gland cortex	UBERON:0035827	93.37	gold quality
ileal mucosa	UBERON:0000331	93.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.07	gold quality
ganglionic eminence	UBERON:0004023	93.04	gold quality
cortex of kidney	UBERON:0001225	92.47	gold quality
adult mammalian kidney	UBERON:0000082	92.46	gold quality
adenohypophysis	UBERON:0002196	92.42	gold quality
heart left ventricle	UBERON:0002084	92.26	gold quality
pituitary gland	UBERON:0000007	92.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	370.09
E-HCAD-13	yes	20.96
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 9)

• Results suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway. (PMID:19521662)
• In patients with short-rib polydactyly syndrome type III, primary cilia in WDR34 mutant fibroblasts were significantly shorter than normal and had a bulbous tip. (PMID:24183449)
• Mutations in WDR34 cause Jeune asphyxiating thoracic dystrophy. WDR34 is critical for ciliary functions essential to normal development and survival. (PMID:24183451)
• In addition to the in vitro experiments, WDR34 negativity was correlated with tumoral growth of OSCCs. Our findings suggested that WDR34 inhibits OSCC progression and might be a potential tumor-suppressor molecule in OSCCs. (PMID:29278705)
• loss of function of dynein-2 WDR34 and WDR60 subunits leads to defects in transition zone architecture, as well as intraflagellar transport. (PMID:30320547)
• these results indicate that incorporation of DYNLL1/DYNLL2 and DYNLRB1/DYNLRB2 into the dynein-2 complex via interactions with the WDR34 intermediate chain is crucial for dynein-2 function in retrograde ciliary protein trafficking. (PMID:30649997)
• Our study revealed that WDR34 promoted the progression of HCC by activating Wnt/beta-catenin signaling. (PMID:30877610)
• WDR34 mutation from anencephaly patients impaired both SHH and PCP signaling pathways. (PMID:32576942)
• WDR34, a candidate gene for non-syndromic rod-cone dystrophy. (PMID:33124039)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dync2i2	ENSDARG00000057635
mus_musculus	Dync2i2	ENSMUSG00000039715
rattus_norvegicus	Dync2i2	ENSRNOG00000015636

Paralogs (7): DYNC1I2 (ENSG00000077380), DNAI1 (ENSG00000122735), DYNC2I1 (ENSG00000126870), DNAI4 (ENSG00000152763), DYNC1I1 (ENSG00000158560), DNAI3 (ENSG00000162643), DNAI2 (ENSG00000171595)

Protein

Protein identifiers

Cytoplasmic dynein 2 intermediate chain 2 — Q96EX3 (reviewed: Q96EX3)

Alternative names: Dynein 2 intermediate chain 2, WD repeat-containing protein 34

All UniProt accessions (2): Q96EX3, A2A3F8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system. DYNC2I2 plays a major role in retrograde ciliary protein trafficking and in ciliogenesis. Required also to maintain a functional transition zone. Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Inhibits the MAP3K7-induced NF-kappa-B activation pathway. Inhibits MAP3K7 phosphorylation at ‘Thr-184’ and ‘Thr-187’ upon Il-1 beta stimulation.

Subunit / interactions. The cytoplasmic dynein 2 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs). Among them, a heavy chain (DYNC2H1), two intermediate chains (DYNC2I2 and DYNC2I1), a light intermediate chain (DYNC2LI1), and a light chain (DYNLT2B) are unique to the cytoplasmic dynein complex 2, but a subset of the light chains are also shared by dynein-1 and dynein-2 complexes. Interacts with DYNC2I1; their C-terminal domains each bind a copy of the heavy chain, and their extended N-terminal regions are held together by an array of light chain dimers. Interacts with DYNLL2; this interaction is essential for dynein-2-mediated retrograde trafficking of ciliary proteins. Interacts with DYNLRB1; this interaction is essential for dynein-2-mediated retrograde trafficking of ciliary proteins. Interacts (via the WD domains) with MAP3K7 and TAB3. Interacts (via WD domains) with TAB2 (via C-terminus). Interacts (via WD domains) with TRAF6 (via TRAF-type domains).

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body. Cilium axoneme. Microtubule organizing center. Centrosome. Cell projection. Cilium. Filopodium.

Tissue specificity. Expressed in several cell lines (at protein level).

Disease relevance. Short-rib thoracic dysplasia 11 with or without polydactyly (SRTD11) [MIM:615633] A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a ’trident’ appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the dynein light intermediate chain family.

RefSeq proteins (1): NP_443076* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050687	Dynein_IC	Family

Pfam: PF00400

UniProt features (23 total): sequence variant 12, repeat 5, sequence conflict 2, region of interest 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6SC2	ELECTRON MICROSCOPY	3.9
8RGH	ELECTRON MICROSCOPY	3.9
8RGG	ELECTRON MICROSCOPY	4
6RLB	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EX3-F1	82.66	0.65

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): 15

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 349 (showing top): YY1_Q6, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, YY1_01, GOBP_CELL_PROJECTION_ORGANIZATION, MODULE_397, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, CUI_TCF21_TARGETS_2_UP, GOCC_FILOPODIUM, GOCC_CENTRIOLE, GOCC_CYTOPLASMIC_REGION, NUYTTEN_EZH2_TARGETS_DN, GOCC_GERM_CELL_NUCLEUS

GO Biological Process (3): intraciliary retrograde transport (GO:0035721), intraciliary transport (GO:0042073), cilium assembly (GO:0060271)

GO Molecular Function (3): dynein light chain binding (GO:0045503), dynein heavy chain binding (GO:0045504), protein binding (GO:0005515)

GO Cellular Component (17): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cytoplasmic dynein complex (GO:0005868), cilium (GO:0005929), axoneme (GO:0005930), nuclear body (GO:0016604), filopodium (GO:0030175), nuclear membrane (GO:0031965), ciliary basal body (GO:0036064), ciliary plasm (GO:0097014), ciliary tip (GO:0097542), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cilium	4
intracellular membraneless organelle	4
microtubule organizing center	3
cilium organization	2
protein binding	2
nuclear lumen	2
cytoplasm	2
intraciliary transport	1
transport along microtubule	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
binding	1
intracellular anatomical structure	1
centriole	1
dynein complex	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
nucleoplasm	1
actin-based cell projection	1
nucleus	1
nuclear envelope	1
organelle membrane	1

Protein interactions and networks

STRING

945 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNC2I2	DYNC2H1	Q8NCM8	971
DYNC2I2	DYNLT2B	Q8WW35	874
DYNC2I2	DYNC2LI1	Q8TCX1	874
DYNC2I2	DYNLL1	P63167	820
DYNC2I2	DYNLL2	Q96FJ2	784
DYNC2I2	TAB3	Q8N5C8	778
DYNC2I2	IFT140	Q96RY7	757
DYNC2I2	WDR19	Q8NEZ3	756
DYNC2I2	WDR35	Q9P2L0	750
DYNC2I2	IFT43	Q96FT9	743
DYNC2I2	DYNC2I1	Q8WVS4	706
DYNC2I2	IFT80	Q9P2H3	689
DYNC2I2	TTC21B	Q7Z4L5	688
DYNC2I2	IFT172	Q9UG01	683
DYNC2I2	IFT122	Q9HBG6	663

IntAct

65 interactions, top by confidence:

A	B	Type	Score
DYNC2I1	DYNC2I2	psi-mi:“MI:0915”(physical association)	0.840
DYNC2I2	DYNC2I1	psi-mi:“MI:0915”(physical association)	0.840
DYNLT2B	DYNLT1	psi-mi:“MI:0914”(association)	0.790
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNC2I1	DYNLL1	psi-mi:“MI:0915”(physical association)	0.700
DYNLT1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.640
DYNC2I2	DYNLL1	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
DYNC2I2	COIL	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	DYNC2I2	psi-mi:“MI:0915”(physical association)	0.560
DYNC2I2	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
COIL	DYNC2I2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	DYNC2I2	psi-mi:“MI:0915”(physical association)	0.560
DYNC2I2	TCP1	psi-mi:“MI:0914”(association)	0.530
DYNLT2B	SNX2	psi-mi:“MI:0914”(association)	0.530
DYNLL1	SHMT2	psi-mi:“MI:0914”(association)	0.510
DYNLL2	SHMT2	psi-mi:“MI:0914”(association)	0.510
DYNLRB2	PAFAH1B1	psi-mi:“MI:0914”(association)	0.510
DYNLT2B	TIPRL	psi-mi:“MI:0914”(association)	0.510
DYNC2I1	ZRANB2	psi-mi:“MI:0914”(association)	0.510
Dynll1		psi-mi:“MI:0915”(physical association)	0.400
DYNC2I2	UXT	psi-mi:“MI:0915”(physical association)	0.400
MAPK6	DYNC2I2	psi-mi:“MI:0915”(physical association)	0.370
Dynlrb1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
DYNC1I1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.350

BioGRID (89): WDR34 (Two-hybrid), WDR34 (Two-hybrid), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Proximity Label-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), WDR34 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB9, A2RRH5, A2RUS2, O43379, O60336, P58742, Q08BB3, Q0VBY8, Q148I1, Q15334, Q3MHH0, Q3SZD4, Q3U3T8, Q499N3, Q4R3J7, Q4VBE8, Q5FW06, Q5QP82, Q5RCX2, Q5T6F0, Q5U4D9, Q5U4F6, Q5VW00, Q5ZJL7, Q63ZP7, Q6AX81, Q6AY87, Q6NS57, Q6NWH1, Q6P1M3, Q6P809, Q7Z5U6, Q80Y17, Q86W42, Q8AVS9, Q8BGW4, Q8BGZ3, Q8C5V5, Q8HXL3, Q8K4K5

Diamond homologs: Q5U4F6, Q96EX3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
Intraflagellar transport	8	43.3×	2e-09
COPI-independent Golgi-to-ER retrograde traffic	5	28.1×	1e-04
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	26.2×	1e-04
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	5	15.8×	6e-04
RHO GTPases Activate Formins	6	12.6×	4e-04
EML4 and NUDC in mitotic spindle formation	5	12.6×	2e-03
Resolution of Sister Chromatid Cohesion	5	11.7×	2e-03
Mitotic Prometaphase	5	9.3×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
microtubule-based movement	6	34.8×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	10
Uncertain significance	253
Likely benign	245
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323763	NM_052844.4(DYNC2I2):c.1315_1318del (p.Phe439fs)	Pathogenic
1681194	NM_052844.4(DYNC2I2):c.1198_1201dup (p.Ser401fs)	Pathogenic
1681251	NM_052844.4(DYNC2I2):c.347_348del (p.Glu116fs)	Pathogenic
1911444	NM_052844.4(DYNC2I2):c.447_448del (p.Thr151fs)	Pathogenic
2051598	NM_052844.4(DYNC2I2):c.361C>T (p.Arg121Ter)	Pathogenic
2057434	NM_052844.4(DYNC2I2):c.1117_1118del (p.Arg373fs)	Pathogenic
2109376	NM_052844.4(DYNC2I2):c.955del (p.Leu319fs)	Pathogenic
2112236	NM_052844.4(DYNC2I2):c.1294C>T (p.Gln432Ter)	Pathogenic
2135286	NM_052844.4(DYNC2I2):c.245_246del (p.His82fs)	Pathogenic
2198627	NM_052844.4(DYNC2I2):c.1313dup (p.Phe439fs)	Pathogenic
2423787	NC_000009.11:g.(?131329020)(131419005_?)del	Pathogenic
2703951	NM_052844.4(DYNC2I2):c.1461_1464dup (p.Glu489fs)	Pathogenic
2718602	NM_052844.4(DYNC2I2):c.1315_1318dup (p.Ala440fs)	Pathogenic
2806411	NM_052844.4(DYNC2I2):c.1531C>T (p.Gln511Ter)	Pathogenic
2815325	NM_052844.4(DYNC2I2):c.51_64dup (p.Ala22fs)	Pathogenic
2872998	NM_052844.4(DYNC2I2):c.1509_1515del (p.Gln504_Gly505insTer)	Pathogenic
2885703	NM_052844.4(DYNC2I2):c.256del (p.Gln86fs)	Pathogenic
2899243	NM_052844.4(DYNC2I2):c.1171dup (p.His391fs)	Pathogenic
3063124	GRCh37/hg19 9q34.11(chr9:131282253-131530589)x1	Pathogenic
3661883	NM_052844.4(DYNC2I2):c.33_36del (p.Ser11fs)	Pathogenic
3684732	NM_052844.4(DYNC2I2):c.1284_1305dup (p.Lys436fs)	Pathogenic
4532118	NM_052844.4(DYNC2I2):c.1193_1194del (p.Val398fs)	Pathogenic
4711218	NM_052844.4(DYNC2I2):c.1280_1283del (p.Pro427fs)	Pathogenic
4724808	NM_052844.4(DYNC2I2):c.263_303dup (p.Gln102fs)	Pathogenic
4729956	NM_052844.4(DYNC2I2):c.149C>A (p.Ser50Ter)	Pathogenic
4731369	NM_052844.4(DYNC2I2):c.1428del (p.Lys477fs)	Pathogenic
4763097	NM_052844.4(DYNC2I2):c.1206del (p.Phe403fs)	Pathogenic
576613	NM_052844.4(DYNC2I2):c.26del (p.Pro9fs)	Pathogenic
583607	NC_000009.12:g.(?128632127)(128640939_?)del	Pathogenic
97037	NM_052844.4(DYNC2I2):c.1022C>T (p.Ala341Val)	Pathogenic

SpliceAI

1740 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128633978:GTCAC:G	acceptor_gain	1.0000
9:128633979:TCAC:T	acceptor_gain	1.0000
9:128633980:CAC:C	acceptor_gain	1.0000
9:128633980:CACC:C	acceptor_gain	1.0000
9:128633981:AC:A	acceptor_gain	1.0000
9:128633981:ACCT:A	acceptor_loss	1.0000
9:128633982:CC:C	acceptor_gain	1.0000
9:128633983:C:CA	acceptor_loss	1.0000
9:128633983:C:CC	acceptor_gain	1.0000
9:128633986:C:CT	acceptor_gain	1.0000
9:128634685:GTA:G	donor_loss	1.0000
9:128634920:TG:T	acceptor_gain	1.0000
9:128635088:GTACC:G	donor_loss	1.0000
9:128635089:TA:T	donor_loss	1.0000
9:128635091:CCTT:C	donor_gain	1.0000
9:128636275:GCTCA:G	donor_loss	1.0000
9:128636276:CTCAC:C	donor_loss	1.0000
9:128636277:TCACC:T	donor_loss	1.0000
9:128636278:CA:C	donor_loss	1.0000
9:128636434:CCAGC:C	acceptor_gain	1.0000
9:128636435:CAGC:C	acceptor_gain	1.0000
9:128636435:CAGCC:C	acceptor_gain	1.0000
9:128636436:AGC:A	acceptor_gain	1.0000
9:128636437:GC:G	acceptor_gain	1.0000
9:128636437:GCC:G	acceptor_loss	1.0000
9:128636438:CC:C	acceptor_gain	1.0000
9:128636439:C:CC	acceptor_gain	1.0000
9:128636439:CTGT:C	acceptor_loss	1.0000
9:128636440:T:A	acceptor_loss	1.0000
9:128640690:CCAT:C	donor_gain	1.0000

AlphaMissense

3459 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128635209:A:C	S288R	0.999
9:128635209:A:T	S288R	0.999
9:128635211:T:G	S288R	0.999
9:128634271:A:G	W443R	0.998
9:128634271:A:T	W443R	0.998
9:128636958:A:G	W169R	0.997
9:128636958:A:T	W169R	0.997
9:128635253:A:G	W274R	0.993
9:128635253:A:T	W274R	0.993
9:128635752:C:A	G240V	0.993
9:128636392:A:G	W198R	0.993
9:128636392:A:T	W198R	0.993
9:128633885:G:C	F490L	0.992
9:128633885:G:T	F490L	0.992
9:128633887:A:G	F490L	0.992
9:128634368:G:C	S410R	0.992
9:128634368:G:T	S410R	0.992
9:128634370:T:G	S410R	0.992
9:128633853:C:T	G501D	0.991
9:128633859:G:T	A499D	0.991
9:128634243:G:T	A452E	0.988
9:128633827:A:G	W510R	0.987
9:128633827:A:T	W510R	0.987
9:128635738:A:G	W245R	0.987
9:128635738:A:T	W245R	0.987
9:128636956:C:A	W169C	0.987
9:128636956:C:G	W169C	0.987
9:128634269:C:A	W443C	0.986
9:128634269:C:G	W443C	0.986
9:128635764:C:T	G236E	0.986

dbSNP variants (sampled 300 via entrez): RS1000012576 (9:128641296 C>A,G,T), RS1000054665 (9:128656725 A>C,G), RS1000087141 (9:128641156 T>A), RS1000127877 (9:128656611 T>C,G), RS1000193943 (9:128646777 C>T), RS1000213963 (9:128671054 C>G,T), RS1000285526 (9:128662694 T>C), RS1000347105 (9:128654997 G>A), RS1000451084 (9:128647778 G>A), RS1000465960 (9:128654431 C>G), RS1000466700 (9:128669343 C>A,T), RS1000581341 (9:128666970 G>A,C,T), RS1000609945 (9:128647074 G>C), RS1000625592 (9:128661578 G>A,C,T), RS1000693595 (9:128662871 T>C)

Disease associations

OMIM: gene MIM:613363 | disease phenotypes: MIM:615633, MIM:613477, MIM:208500, MIM:613091, MIM:618106

GenCC curated gene-disease

Disease	Classification	Inheritance
short-rib thoracic dysplasia 11 with or without polydactyly	Definitive	Autosomal recessive
Jeune syndrome	Supportive	Autosomal recessive
short rib-polydactyly syndrome, Verma-Naumoff type	Supportive	Autosomal recessive
retinitis pigmentosa	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
short-rib thoracic dysplasia 11 with or without polydactyly	Definitive	AR

Mondo (9): short-rib thoracic dysplasia 11 with or without polydactyly (MONDO:0014287), inherited retinal dystrophy (MONDO:0019118), developmental and epileptic encephalopathy (MONDO:0100620), developmental and epileptic encephalopathy, 5 (MONDO:0013277), Jeune syndrome (MONDO:0018770), asphyxiating thoracic dystrophy 3 (MONDO:0013127), intellectual disability, autosomal dominant 58 (MONDO:0020847), (MONDO:0019664), retinitis pigmentosa (MONDO:0019200)

Orphanet (6): Jeune syndrome (Orphanet:474), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Short rib-polydactyly syndrome, Verma-Naumoff type (Orphanet:93271), West syndrome (Orphanet:3451), Short rib-polydactyly syndrome, Majewski type (Orphanet:93269), Short rib-polydactyly syndrome, Saldino-Noonan type (Orphanet:93270)

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000062	Ambiguous genitalia
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000090	Nephronophthisis
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000121	Nephrocalcinosis
HP:0000126	Hydronephrosis
HP:0000204	Cleft upper lip
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000445	Wide nose
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000750	Delayed speech and language development
HP:0000766	Abnormal sternum morphology
HP:0000772	Abnormal rib morphology
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000888	Horizontal ribs
HP:0000889	Abnormal clavicle morphology
HP:0000895	Lateral clavicle hook
HP:0000944	Abnormal metaphysis morphology
HP:0001156	Brachydactyly
HP:0001162	Postaxial hand polydactyly
HP:0001177	Preaxial hand polydactyly

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001959_7	Eating disorders (purging via substances)	5.000000e-06
GCST002115_14	Axial length	6.000000e-06
GCST005951_65	Body mass index	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement
EFO:0004340	body mass index

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C537571	Jeune syndrome (supp.)
C537602	Short rib-polydactyly syndrome, Verma-Naumoff type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects expression, affects methylation, decreases expression, increases abundance	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	decreases methylation	1
ferrous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2W4	Abcam HEK293T DYNC2I2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)