DYNC2I1

Summary

DYNC2I1 (dynein 2 intermediate chain 1, HGNC:21862) is a protein-coding gene on chromosome 7q36.3, encoding Cytoplasmic dynein 2 intermediate chain 1 (Q8WVS4). 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) and may facilitate the 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. The encoded protein contains four WD repeats and may play a role in the formation of cilia. Mutations in this gene have been associated with short-rib polydactyly and Jeune syndromes.

Source: NCBI Gene 55112 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short-rib thoracic dysplasia 8 with or without polydactyly (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 705 total — 23 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 77
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_018051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21862
Approved symbol	DYNC2I1
Name	dynein 2 intermediate chain 1
Location	7q36.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10300, FAP163, CFAP163, DIC6
Ensembl gene	ENSG00000126870
Ensembl biotype	protein_coding
OMIM	615462
Entrez	55112

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000397143, ENST00000407559, ENST00000444851, ENST00000454771, ENST00000467220, ENST00000860810, ENST00000860811, ENST00000860812, ENST00000860813, ENST00000860814, ENST00000936430, ENST00000961350, ENST00000961351, ENST00000961352

RefSeq mRNA: 6 — MANE Select: NM_018051 NM_001350914, NM_001350915, NM_001350916, NM_001350917, NM_001350918, NM_018051

CCDS: CCDS47757

Canonical transcript exons

ENST00000407559 — 25 exons

Exon	Start	End
ENSE00001178856	158879684	158879989
ENSE00001178860	158902376	158902595
ENSE00001178869	158876609	158876691
ENSE00001390181	158884564	158884619
ENSE00001600014	158871142	158871562
ENSE00001740767	158869855	158869908
ENSE00001780424	158856558	158856750
ENSE00003458308	158901739	158901816
ENSE00003458351	158905989	158906091
ENSE00003484662	158945581	158946189
ENSE00003485581	158922377	158922549
ENSE00003496860	158930455	158930515
ENSE00003503254	158926187	158926300
ENSE00003506021	158887021	158887075
ENSE00003507007	158941925	158942148
ENSE00003508150	158934418	158934549
ENSE00003522859	158923571	158923733
ENSE00003525112	158914233	158914321
ENSE00003568381	158912985	158913096
ENSE00003579829	158911550	158911679
ENSE00003581435	158926402	158926463
ENSE00003603356	158926992	158927043
ENSE00003606007	158891265	158891333
ENSE00003624224	158934129	158934228
ENSE00003639147	158918740	158918869

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.2825 / max 645.9126, expressed in 1788 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82323	17.2652	1785
82324	1.0173	484

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.47	gold quality
right uterine tube	UBERON:0001302	96.97	gold quality
sperm	CL:0000019	93.83	gold quality
male germ cell	CL:0000015	92.74	gold quality
calcaneal tendon	UBERON:0003701	92.10	gold quality
left testis	UBERON:0004533	91.67	gold quality
tibia	UBERON:0000979	91.57	gold quality
middle temporal gyrus	UBERON:0002771	91.56	gold quality
endothelial cell	CL:0000115	90.74	gold quality
right testis	UBERON:0004534	90.62	gold quality
testis	UBERON:0000473	90.45	gold quality
tendon	UBERON:0000043	90.16	gold quality
apex of heart	UBERON:0002098	89.95	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.38	gold quality
right atrium auricular region	UBERON:0006631	88.12	gold quality
bronchial epithelial cell	CL:0002328	87.93	gold quality
primary visual cortex	UBERON:0002436	87.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.38	gold quality
lower esophagus	UBERON:0013473	87.35	gold quality
epithelium of bronchus	UBERON:0002031	87.28	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.05	gold quality
bronchus	UBERON:0002185	87.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.88	gold quality
cardiac atrium	UBERON:0002081	86.80	gold quality
mucosa of stomach	UBERON:0001199	86.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.69	gold quality
tendon of biceps brachii	UBERON:0008188	86.64	gold quality
gastrocnemius	UBERON:0001388	86.60	gold quality
heart left ventricle	UBERON:0002084	86.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting DYNC2I1, 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-371B-5P	99.99	75.34	4759
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4436B-5P	96.71	68.37	1346

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis. (PMID:23910462)
• exome analysis allowed to identify mutations not previously reported in the DYNC2H1 (MIM 603297) and WDR60 (MIM 615462) genes, both codifying for ciliary intraflagellar transport components whose mutations are known to cause Jeune syndrome (PMID:26874042)
• Our finding broadens the spectrum of WDR60-related phenotypes and shows the utility of broad multigene panels during the genetic work-up of patients with ciliopathies. (PMID:29271569)
• WDR60 plays a major role and TCTEX1D2 plays an auxiliary role in the dynein-2 complex to mediate retrograde ciliary protein trafficking. (PMID:29742051)
• loss of function of dynein-2 WDR34 and WDR60 subunits leads to defects in transition zone architecture, as well as intraflagellar transport. (PMID:30320547)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dync2i1	ENSDARG00000076934
mus_musculus	Dync2i1	ENSMUSG00000042050
rattus_norvegicus	Dync2i1	ENSRNOG00000004520
caenorhabditis_elegans		WBGENE00016165

Paralogs (7): DYNC1I2 (ENSG00000077380), DYNC2I2 (ENSG00000119333), DNAI1 (ENSG00000122735), DNAI4 (ENSG00000152763), DYNC1I1 (ENSG00000158560), DNAI3 (ENSG00000162643), DNAI2 (ENSG00000171595)

Protein

Protein identifiers

Cytoplasmic dynein 2 intermediate chain 1 — Q8WVS4 (reviewed: Q8WVS4)

Alternative names: Dynein 2 intermediate chain 1, WD repeat-containing protein 60

All UniProt accessions (5): Q8WVS4, A0A140VK66, H7BYQ2, H7C022, H7C1E8

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. DYNC2I1 plays a major role in retrograde ciliary protein trafficking in cilia and flagella. Also requires to maintain a functional transition zone.

Subunit / interactions. Intermediate chain of the cytoplasmic dynein complex 2, a multisubunit complex, composed at least of eleven different proteins. 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 DYNC2I2; 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 DYNLT2B. Interacts (via the N-terminal half) with DYNLT2B-DYNLT1 dimer or with DYNLT2B-DYNLT3 dimer; this interaction is crucial for retrograde trafficking of ciliary proteins.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed in chondrocytes (at protein level).

Disease relevance. Short-rib thoracic dysplasia 8 with or without polydactyly (SRTD8) [MIM:615503] 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. Fibroblasts from affected individuals exhibit a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme.

Similarity. Belongs to the dynein light intermediate chain family.

RefSeq proteins (6): NP_001337843, NP_001337844, NP_001337845, NP_001337846, NP_001337847, NP_060521* (*=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
IPR042505	DYNC2I1	Family

UniProt features (25 total): compositionally biased region 8, sequence variant 5, repeat 4, region of interest 3, modified residue 2, sequence conflict 2, chain 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-Q8WVS4-F1	62.87	0.26

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 (2): 30, 247

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 340 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_ORGANELLE_ASSEMBLY, GOBP_EMBRYO_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION, MODULE_48, MODULE_95

GO Biological Process (5): intraciliary retrograde transport (GO:0035721), embryonic skeletal system morphogenesis (GO:0048704), cilium assembly (GO:0060271), cell projection organization (GO:0030030), intraciliary transport (GO:0042073)

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

GO Cellular Component (14): pericentriolar material (GO:0000242), obsolete extracellular space (GO:0005615), centrosome (GO:0005813), cytosol (GO:0005829), cytoplasmic dynein complex (GO:0005868), cilium (GO:0005929), ciliary basal body (GO:0036064), ciliary tip (GO:0097542), ciliary base (GO:0097546), spindle pole (GO:0000922), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), interphase microtubule organizing center (GO:0031021), 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	7
cilium	4
microtubule organizing center	3
cilium organization	2
protein binding	2
intraciliary transport	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	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
cellular component organization	1
transport along microtubule	1
binding	1
centrosome	1
centriole	1
cytoplasm	1
dynein complex	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
ciliary transition zone	1
ciliary transition fiber	1
spindle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

823 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNC2I1	DYNLT2B	Q8WW35	922
DYNC2I1	DYNC2H1	Q8NCM8	904
DYNC2I1	DYNC2LI1	Q8TCX1	883
DYNC2I1	DYNLT1	P63172	775
DYNC2I1	DYNLL1	P63167	761
DYNC2I1	WDR19	Q8NEZ3	721
DYNC2I1	TTC21B	Q7Z4L5	714
DYNC2I1	DYNC2I2	Q96EX3	706
DYNC2I1	ESYT2	A0FGR8	703
DYNC2I1	WDR35	Q9P2L0	698
DYNC2I1	IFT140	Q96RY7	698
DYNC2I1	IFT172	Q9UG01	681
DYNC2I1	IFT80	Q9P2H3	675
DYNC2I1	IFT43	Q96FT9	649
DYNC2I1	DYNLRB1	Q9NP97	646

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
DYNC2I1	NUDC	psi-mi:“MI:0915”(physical association)	0.660
DYNLT1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.640
NUDC	DNAJB1	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
BNIP1	NBAS	psi-mi:“MI:0914”(association)	0.640
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
DYNLT2B	SNX2	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
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
HMGB1	DYNC2I1	psi-mi:“MI:0915”(physical association)	0.370
DYNC2I1	TK1	psi-mi:“MI:0915”(physical association)	0.370
Shoc2	GABPB1	psi-mi:“MI:0914”(association)	0.350
Sgo2a	GPA33	psi-mi:“MI:0914”(association)	0.350
Dynlrb1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.350
TENT5A	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Proximity Label-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), TCTEX1D2 (Affinity Capture-MS)

ESM2 similar proteins: A2AJT4, A2CG63, B0S733, F1QNX7, G3V8T1, O75376, O94988, P29536, Q02040, Q14241, Q149C2, Q15695, Q15696, Q28G87, Q2KIC0, Q4FZU3, Q4G0J3, Q4KKX4, Q4LE39, Q4R627, Q53F19, Q561R3, Q5NCR9, Q5R4U2, Q5RL73, Q5U2T3, Q5XIN3, Q5ZM19, Q60974, Q62377, Q63187, Q64707, Q6PFK1, Q6PGZ3, Q8BZR9, Q8C761, Q8CB77, Q8K2X2, Q8QG78, Q8TDR0

Diamond homologs: Q8C761, Q8WVS4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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	6	28.0×	2e-05
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	22.5×	4e-04
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	5	13.6×	2e-03
RHO GTPases Activate Formins	6	10.8×	2e-03
EML4 and NUDC in mitotic spindle formation	5	10.8×	5e-03
Resolution of Sister Chromatid Cohesion	5	10.1×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
microtubule-based movement	5	25.9×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	12
Uncertain significance	307
Likely benign	241
Benign	76

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1076069	NM_018051.5(DYNC2I1):c.975dup (p.Asp326fs)	Pathogenic
147687	GRCh38/hg38 7q36.3(chr7:157898696-159295947)x3	Pathogenic
1680624	NC_000007.13:g.(?158677235)(158677330_?)del	Pathogenic
1680649	NM_018051.5(DYNC2I1):c.682C>T (p.Arg228Ter)	Pathogenic
1680698	NM_018051.5(DYNC2I1):c.1924C>T (p.Arg642Ter)	Pathogenic
2000055	NM_018051.5(DYNC2I1):c.527_528del (p.Asp175_Ser176insTer)	Pathogenic
2025330	NM_018051.5(DYNC2I1):c.378_381del (p.Asp126fs)	Pathogenic
2162517	NM_018051.5(DYNC2I1):c.712_715del (p.Glu238fs)	Pathogenic
2186983	NM_018051.5(DYNC2I1):c.562C>T (p.Arg188Ter)	Pathogenic
2706914	NM_018051.5(DYNC2I1):c.2378dup (p.Gly794fs)	Pathogenic
2873339	NM_018051.5(DYNC2I1):c.778C>T (p.Arg260Ter)	Pathogenic
3245816	NC_000007.13:g.(?158649427)(158738470_?)del	Pathogenic
4086099	NM_018051.5(DYNC2I1):c.1580dup (p.Asn527fs)	Pathogenic
446629	NM_018051.5(DYNC2I1):c.2284C>T (p.Arg762Ter)	Pathogenic
4719191	NM_018051.5(DYNC2I1):c.2651_2652dup (p.Ile885fs)	Pathogenic
4719425	NM_018051.5(DYNC2I1):c.671del (p.Asp224fs)	Pathogenic
4723080	NM_018051.5(DYNC2I1):c.1647dup (p.Glu550fs)	Pathogenic
563395	GRCh37/hg19 7q36.3(chr7:157714334-159119707)x3	Pathogenic
57308	GRCh38/hg38 7q36.3(chr7:158154429-159135526)x1	Pathogenic
60327	GRCh38/hg38 7q36.3(chr7:158568512-159281301)x1	Pathogenic
88644	NM_018051.5(DYNC2I1):c.1891C>T (p.Gln631Ter)	Pathogenic
88645	NM_018051.5(DYNC2I1):c.2246C>T (p.Thr749Met)	Pathogenic
88646	NM_018051.5(DYNC2I1):c.1703-3T>A	Pathogenic
2631190	NM_018051.5(DYNC2I1):c.553del (p.Arg185fs)	Likely pathogenic
2690779	NM_018051.5(DYNC2I1):c.898C>T (p.Arg300Ter)	Likely pathogenic
3649821	NM_018051.5(DYNC2I1):c.490+1G>A	Likely pathogenic
3780797	NM_018051.5(DYNC2I1):c.1358-2A>G	Likely pathogenic
3906974	NM_018051.5(DYNC2I1):c.265_268del (p.Gln89fs)	Likely pathogenic
4292405	NM_018051.5(DYNC2I1):c.1566_1578del (p.Asn522fs)	Likely pathogenic
437277	NM_018051.5(DYNC2I1):c.1162del (p.Cys388fs)	Likely pathogenic

SpliceAI

5345 predictions. Top by Δscore:

Variant	Effect	Δscore
7:158871550:A:T	donor_gain	1.0000
7:158871558:CTCAG:C	donor_loss	1.0000
7:158871559:TCAG:T	donor_loss	1.0000
7:158871560:CAGGT:C	donor_loss	1.0000
7:158871561:AGG:A	donor_loss	1.0000
7:158871562:GGTG:G	donor_loss	1.0000
7:158871563:G:A	donor_loss	1.0000
7:158871564:T:A	donor_loss	1.0000
7:158876608:GTAA:G	acceptor_gain	1.0000
7:158876730:TTGCC:T	donor_gain	1.0000
7:158884620:G:GG	donor_gain	1.0000
7:158884681:G:T	donor_gain	1.0000
7:158884719:C:T	donor_gain	1.0000
7:158884726:T:G	donor_gain	1.0000
7:158887073:AAG:A	donor_loss	1.0000
7:158887074:AGGT:A	donor_loss	1.0000
7:158887076:GTAA:G	donor_loss	1.0000
7:158887077:T:G	donor_loss	1.0000
7:158890516:G:GT	donor_gain	1.0000
7:158901738:GGAA:G	acceptor_gain	1.0000
7:158901813:TGAAG:T	donor_loss	1.0000
7:158901814:G:GT	donor_gain	1.0000
7:158901814:GAA:G	donor_gain	1.0000
7:158901814:GAAG:G	donor_loss	1.0000
7:158901815:AA:A	donor_gain	1.0000
7:158901815:AAGT:A	donor_loss	1.0000
7:158901816:AGTA:A	donor_loss	1.0000
7:158901817:G:C	donor_loss	1.0000
7:158901817:GTAT:G	donor_gain	1.0000
7:158901818:T:G	donor_loss	1.0000

AlphaMissense

7067 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:158926461:T:A	W811R	0.998
7:158926461:T:C	W811R	0.998
7:158923646:T:A	W724R	0.997
7:158923646:T:C	W724R	0.997
7:158942030:T:A	W962R	0.997
7:158942030:T:C	W962R	0.997
7:158911656:T:C	F523L	0.996
7:158911658:T:A	F523L	0.996
7:158911658:T:G	F523L	0.996
7:158911635:T:C	Y516H	0.994
7:158911644:T:G	Y519D	0.994
7:158922496:T:A	W681R	0.994
7:158922496:T:C	W681R	0.994
7:158911555:G:C	R489P	0.993
7:158911660:G:A	G524E	0.993
7:158914301:T:C	F591L	0.993
7:158914303:T:A	F591L	0.993
7:158914303:T:G	F591L	0.993
7:158923724:T:C	F750L	0.993
7:158923726:T:A	F750L	0.993
7:158923726:T:G	F750L	0.993
7:158911576:T:C	L496P	0.992
7:158922498:G:C	W681C	0.992
7:158922498:G:T	W681C	0.992
7:158902502:G:C	A422P	0.991
7:158911567:T:C	L493P	0.991
7:158914314:C:A	A595D	0.991
7:158923589:A:C	S705R	0.991
7:158923591:C:A	S705R	0.991
7:158923591:C:G	S705R	0.991

dbSNP variants (sampled 300 via entrez): RS1000019793 (7:158854840 A>G), RS1000061929 (7:158905978 C>A,T), RS1000074148 (7:158890522 C>A,T), RS1000080690 (7:158857197 T>C), RS1000104766 (7:158929724 C>A,T), RS1000146729 (7:158928297 T>G), RS1000153682 (7:158941093 A>T), RS1000191744 (7:158860110 C>T), RS1000207903 (7:158901975 C>T), RS1000216938 (7:158891634 A>C), RS1000218509 (7:158938661 C>A), RS1000266311 (7:158882020 T>G), RS1000275830 (7:158934659 C>A,T), RS1000287895 (7:158860325 C>T), RS1000295176 (7:158867369 T>C)

Disease associations

OMIM: gene MIM:615462 | disease phenotypes: MIM:615503, MIM:208500, MIM:613091

GenCC curated gene-disease

Disease	Classification	Inheritance
short-rib thoracic dysplasia 8 with or without polydactyly	Definitive	Autosomal recessive
Jeune syndrome	Supportive	Autosomal recessive
short rib-polydactyly syndrome, Verma-Naumoff type	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
short-rib thoracic dysplasia 8 with or without polydactyly	Definitive	AR

Mondo (4): short-rib thoracic dysplasia 8 with or without polydactyly (MONDO:0014214), Jeune syndrome (MONDO:0018770), asphyxiating thoracic dystrophy 3 (MONDO:0013127), (MONDO:0019664)

Orphanet (4): Short rib-polydactyly syndrome, Verma-Naumoff type (Orphanet:93271), Jeune syndrome (Orphanet:474), 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: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:0000518	Cataract
HP:0000766	Abnormal sternum morphology
HP:0000772	Abnormal rib morphology
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000889	Abnormal clavicle morphology
HP:0000895	Lateral clavicle hook
HP:0000944	Abnormal metaphysis morphology
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001162	Postaxial hand polydactyly
HP:0001177	Preaxial hand polydactyly
HP:0001274	Agenesis of corpus callosum
HP:0001305	Dandy-Walker malformation
HP:0001321	Cerebellar hypoplasia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000176_17	Height	3.000000e-07
GCST010002_267	Refractive error	2.000000e-37
GCST011380_4	Cutaneous mastocytosis (adult)	1.000000e-07
GCST011920_2	Hearing loss in noise exposure	2.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
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

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	2
FR900359	decreases phosphorylation	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, 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	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Cadmium	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Oxygen	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00948376	Not specified	COMPLETED	Natural History of Asphyxiating Thoracic Dystrophy (DTJ)
NCT04143841	Not specified	TERMINATED	Viveye Ocular Magnetic Neurostimulation System (OMNS) for the Management of Severe Dry Eye Disease
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)