DYNC2LI1

Summary

DYNC2LI1 (dynein cytoplasmic 2 light intermediate chain 1, HGNC:24595) is a protein-coding gene on chromosome 2p21, encoding Cytoplasmic dynein 2 light intermediate chain 1 (Q8TCX1). 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, fa….

This gene encodes a protein that is a component of the dynein-2 microtubule motor protein complex that plays a role in the retrograde transport of cargo in primary cilia via the intraflagellar transport system. This gene is ubiquitously expressed and its protein, which localizes to the axoneme and Golgi apparatus, interacts directly with the cytoplasmic dynein 2 heavy chain 1 protein to form part of the multi-protein dynein-2 complex. Mutations in this gene produce defects in the dynein-2 complex which result in several types of ciliopathy including short-rib thoracic dysplasia 15 with polydactyly (SRTD15). Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 51626 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short-rib thoracic dysplasia 15 with polydactyly (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 316 total — 14 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 96
• MANE Select transcript: NM_016008

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24595
Approved symbol	DYNC2LI1
Name	dynein cytoplasmic 2 light intermediate chain 1
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	D2LIC, LIC3, CGI-60, DKFZP564A033
Ensembl gene	ENSG00000138036
Ensembl biotype	protein_coding
OMIM	617083
Entrez	51626

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000260605, ENST00000378587, ENST00000398823, ENST00000406852, ENST00000462426, ENST00000479242, ENST00000482738, ENST00000489222, ENST00000496980, ENST00000605786, ENST00000857665, ENST00000857666, ENST00000857667, ENST00000857668, ENST00000857669, ENST00000857670, ENST00000857671, ENST00000911569, ENST00000965101, ENST00000965102, ENST00000965103, ENST00000965104

RefSeq mRNA: 5 — MANE Select: NM_016008 NM_001193464, NM_001348912, NM_001348913, NM_015522, NM_016008

CCDS: CCDS1813, CCDS46270, CCDS62903

Canonical transcript exons

ENST00000260605 — 13 exons

Exon	Start	End
ENSE00000750758	43801639	43801709
ENSE00001005709	43805154	43805246
ENSE00001555602	43774039	43774146
ENSE00001958873	43809705	43810010
ENSE00003465132	43789633	43789721
ENSE00003485418	43796718	43796795
ENSE00003518666	43794457	43794643
ENSE00003526653	43804642	43804739
ENSE00003530077	43800841	43800917
ENSE00003530416	43787181	43787250
ENSE00003549380	43776782	43776899
ENSE00003594774	43783520	43783554
ENSE00003656973	43795890	43795958

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.5992 / max 696.1939, expressed in 1792 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19985	23.7143	1791
19986	0.8849	509

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.16	gold quality
bronchial epithelial cell	CL:0002328	96.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.05	gold quality
calcaneal tendon	UBERON:0003701	95.41	gold quality
epithelium of bronchus	UBERON:0002031	94.89	gold quality
metanephros cortex	UBERON:0010533	94.50	gold quality
bronchus	UBERON:0002185	94.44	gold quality
adenohypophysis	UBERON:0002196	94.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.17	gold quality
adrenal tissue	UBERON:0018303	93.96	gold quality
left ovary	UBERON:0002119	93.94	gold quality
pituitary gland	UBERON:0000007	93.90	gold quality
body of uterus	UBERON:0009853	93.43	gold quality
right testis	UBERON:0004534	93.32	gold quality
left testis	UBERON:0004533	93.23	gold quality
right ovary	UBERON:0002118	93.21	gold quality
germinal epithelium of ovary	UBERON:0001304	93.17	gold quality
endometrium	UBERON:0001295	93.08	gold quality
choroid plexus epithelium	UBERON:0003911	93.04	gold quality
endocervix	UBERON:0000458	93.00	gold quality
oocyte	CL:0000023	92.97	gold quality
nucleus accumbens	UBERON:0001882	92.83	gold quality
ovary	UBERON:0000992	92.46	gold quality
caudate nucleus	UBERON:0001873	92.41	gold quality
testis	UBERON:0000473	92.30	gold quality
pigmented layer of retina	UBERON:0001782	92.24	gold quality
caput epididymis	UBERON:0004358	92.24	gold quality
retina	UBERON:0000966	92.22	gold quality
right frontal lobe	UBERON:0002810	92.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting DYNC2LI1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
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-4500	99.99	72.72	2367
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
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-4715-3P	99.98	66.03	670
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 5)

• DYNC2LI1 is essential for dynein-2 complex stability and that mutations in DYNC2LI1 result in variable length, including hyperelongated, cilia, Hedgehog pathway impairment and ciliary IFT accumulations, causing short rib polydactyly syndrome. (PMID:26077881)
• depletion of DYNC2LI1 induced altered cilia morphology with broadened ciliary tips and accumulation of intraflagellar transport complexes (IFT-B) complex proteins in accordance with retrograde IFT defects. (PMID:26130459)
• Our findings indicate that DYNC2LI1 mutations are associated with a wider clinical spectrum than previously appreciated, including EvC, with the severity of the phenotype likely depending on the extent of defective DYNC2LI1 function. (PMID:28857138)
• Whole-exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy. (PMID:33030252)
• Combinations of deletion and missense variations of the dynein-2 DYNC2LI1 subunit found in skeletal ciliopathies cause ciliary defects. (PMID:34997029)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dync2li1	ENSDARG00000039770
mus_musculus	Dync2li1	ENSMUSG00000024253
rattus_norvegicus	Dync2li1	ENSRNOG00000005151
drosophila_melanogaster	CG3769	FBGN0032119
caenorhabditis_elegans		WBGENE00006960

Protein

Protein identifiers

Cytoplasmic dynein 2 light intermediate chain 1 — Q8TCX1 (reviewed: Q8TCX1)

All UniProt accessions (5): Q8TCX1, E5RFM8, E5RJK4, E5RK97, H7BYC8

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, facilitating the assembly of these organelles. Involved in the regulation of ciliary length.

Subunit / interactions. Light 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 dynein-2 complex, but a subset of light chains are also shared by dynein-1 and dynein-2 complexes. Dynein-2 complex is built around two copies of cytoplasmic dynein 2 heavy chain 1 (DYNC2H1). The C-terminal region of DYNC2H1 forms the motor domain, which converts the energy from ATP hydrolysis into movement. Its N-terminal region forms the tail, an extended structure that binds the other subunits and holds the two heavy chains in a homodimer. Interacts with DYNC2H1 (via N-terminus); this interaction stabilizes the dynein-2 complex structure.

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

Tissue specificity. Expressed in bone, brain, kidney, and cartilage. Lower expression in heart, liver, lung, placenta and thymus.

Disease relevance. Short-rib thoracic dysplasia 15 with polydactyly (SRTD15) [MIM:617088] 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.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8TCX1-1	1	yes
Q8TCX1-2	2
Q8TCX1-3	3
Q8TCX1-4	4
Q8TCX1-5	5

RefSeq proteins (5): NP_001180393, NP_001335841, NP_001335842, NP_056337, NP_057092* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022780	Dynein_light_int_chain	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR040045	DYNC2LI1	Family

Pfam: PF05783

UniProt features (13 total): splice variant 6, sequence variant 5, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCX1-F1	85.49	0.54

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 367 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, MODULE_255, MODULE_317, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, GOBP_CILIUM_ORGANIZATION, BROWNE_HCMV_INFECTION_14HR_DN, GOCC_CENTROSOME, DAZARD_RESPONSE_TO_UV_SCC_UP, GOBP_ORGANELLE_ASSEMBLY, BASAKI_YBX1_TARGETS_DN, GOBP_REGULATION_OF_CILIUM_ASSEMBLY

GO Biological Process (6): determination of left/right symmetry (GO:0007368), intraciliary retrograde transport (GO:0035721), intraciliary transport involved in cilium assembly (GO:0035735), regulation of cilium assembly (GO:1902017), cell projection organization (GO:0030030), cilium assembly (GO:0060271)

GO Molecular Function (2): dynein heavy chain binding (GO:0045504), protein binding (GO:0005515)

GO Cellular Component (22): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), cytoplasmic dynein complex (GO:0005868), microtubule (GO:0005874), cilium (GO:0005929), axoneme (GO:0005930), nuclear speck (GO:0016607), motile cilium (GO:0031514), perinuclear theca (GO:0033011), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), apical part of cell (GO:0045177), sperm midpiece (GO:0097225), sperm annulus (GO:0097227), sperm principal piece (GO:0097228), ciliary tip (GO:0097542), cytoskeleton (GO:0005856), cytoplasmic microtubule (GO:0005881), dynein complex (GO:0030286), 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	9
cilium	4
cytoplasm	3
sperm flagellum	3
intraciliary transport	2
cilium assembly	2
microtubule organizing center	2
cytoskeleton	2
microtubule	2
determination of bilateral symmetry	1
left/right pattern formation	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of organelle assembly	1
cellular component organization	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	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
protein binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centriole	1
dynein complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
ciliary plasm	1
nuclear ribonucleoprotein granule	1
perinuclear region of cytoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYNC2LI1	DYNC2H1	Q8NCM8	981
DYNC2LI1	DYNLT2B	Q8WW35	904
DYNC2LI1	DYNC2I1	Q8WVS4	883
DYNC2LI1	DYNC2I2	Q96EX3	874
DYNC2LI1	WDR35	Q9P2L0	760
DYNC2LI1	DYNLL2	Q96FJ2	751
DYNC2LI1	DYNLL1	P63167	750
DYNC2LI1	WDR19	Q8NEZ3	745
DYNC2LI1	IFT140	Q96RY7	743
DYNC2LI1	IFT80	Q9P2H3	718
DYNC2LI1	IFT122	Q9HBG6	717
DYNC2LI1	IFT172	Q9UG01	715
DYNC2LI1	IFT88	Q13099	713
DYNC2LI1	IFT52	Q9Y366	710
DYNC2LI1	DYNC1LI2	O43237	669

IntAct

30 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
INSYN2A	CHUK	psi-mi:“MI:0914”(association)	0.530
SOD1	DYNC2LI1	psi-mi:“MI:0915”(physical association)	0.500
DYNC2LI1	BAG3	psi-mi:“MI:0914”(association)	0.460
DYNC2LI1	DCTN1	psi-mi:“MI:0403”(colocalization)	0.460
BAG3	SOD1	psi-mi:“MI:0403”(colocalization)	0.430
Tor1aip1	PEX10	psi-mi:“MI:0914”(association)	0.350
Ercc6l	RPL17	psi-mi:“MI:0914”(association)	0.350
Wdr5	MGA	psi-mi:“MI:0914”(association)	0.350
Iffo2	TAGLN2	psi-mi:“MI:0914”(association)	0.350
POLR2F	BDP1	psi-mi:“MI:0914”(association)	0.350
Cenpf	WDR91	psi-mi:“MI:0914”(association)	0.350
Strip1	STK24	psi-mi:“MI:0914”(association)	0.350
Prpf3	PRPF4	psi-mi:“MI:0914”(association)	0.350
DYNC2I1		psi-mi:“MI:0914”(association)	0.350
ARL14EP	ARPC2	psi-mi:“MI:0914”(association)	0.350
DYNC2LI1	DYNLT1	psi-mi:“MI:0914”(association)	0.350
SPACA1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
GYPA	HYKK	psi-mi:“MI:0914”(association)	0.350
PRKY	METTL15	psi-mi:“MI:0914”(association)	0.350
SSR2	PEX1	psi-mi:“MI:0914”(association)	0.350
DYNC2LI1	LAMP2	psi-mi:“MI:0914”(association)	0.350
DYNC2LI1	IZUMO1R	psi-mi:“MI:0914”(association)	0.350
SLC2A2	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), DYNC2H1 (Affinity Capture-MS)

ESM2 similar proteins: A6ZP88, O01757, O13943, O13950, O74366, O74462, O74945, O74995, O94263, O94316, O94330, O94444, O94672, P15303, P32502, P34567, P36617, P41810, P53914, P87115, Q04673, Q08685, Q10414, Q12004, Q19196, Q32KV4, Q500V9, Q54T59, Q6AY43, Q6BL86, Q6CD24, Q6CPH3, Q6CVX9, Q6FIR8, Q6FM46, Q6FSK3, Q6FWA7, Q75B93, Q7SXY4, Q84WI4

Diamond homologs: Q32KV4, Q6AY43, Q7SXY4, Q8K0T2, Q8TCX1, Q7XA07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	12
Uncertain significance	121
Likely benign	97
Benign	43

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1106719	NM_016008.4(DYNC2LI1):c.18_19del (p.Trp7fs)	Pathogenic
2030462	NM_016008.4(DYNC2LI1):c.318dup (p.Arg107fs)	Pathogenic
212764	NM_016008.4(DYNC2LI1):c.993+1G>A	Pathogenic
212768	NM_016008.4(DYNC2LI1):c.993+3A>G	Pathogenic
253218	NM_016008.4(DYNC2LI1):c.619C>T (p.Arg207Ter)	Pathogenic
253219	NM_016008.4(DYNC2LI1):c.659C>T (p.Thr220Ile)	Pathogenic
3247567	NC_000002.11:g.(?44014300)(44031898_?)del	Pathogenic
3414998	NM_022436.3(ABCG5):c.904+1G>A	Pathogenic
4704259	NM_016008.4(DYNC2LI1):c.650del (p.Ser216_Leu217insTer)	Pathogenic
4781143	NM_016008.4(DYNC2LI1):c.518dup (p.Leu173fs)	Pathogenic
518437	NM_016008.4(DYNC2LI1):c.2T>C (p.Met1Thr)	Pathogenic
518438	NM_016008.4(DYNC2LI1):c.420del (p.Lys140_Val141insTer)	Pathogenic
518439	NM_016008.4(DYNC2LI1):c.123_124insA (p.Gly42fs)	Pathogenic
518440	NM_016008.4(DYNC2LI1):c.655-9del	Pathogenic
1468263	NM_022436.3(ABCG5):c.1323_1324+2del	Likely pathogenic
1477816	NM_016008.4(DYNC2LI1):c.127-2A>C	Likely pathogenic
2013260	NM_016008.4(DYNC2LI1):c.802+2T>A	Likely pathogenic
2058731	NM_016008.4(DYNC2LI1):c.961G>T (p.Glu321Ter)	Likely pathogenic
2782763	NM_016008.4(DYNC2LI1):c.127-2A>G	Likely pathogenic
3614925	NM_016008.4(DYNC2LI1):c.900+1G>T	Likely pathogenic
3718484	NM_016008.4(DYNC2LI1):c.900+1G>A	Likely pathogenic
3729390	NM_016008.4(DYNC2LI1):c.126+1G>C	Likely pathogenic
3777991	NM_016008.4(DYNC2LI1):c.9-2A>G	Likely pathogenic
4514263	NM_016008.4(DYNC2LI1):c.731+1G>T	Likely pathogenic
4716072	NM_016008.4(DYNC2LI1):c.127-1G>T	Likely pathogenic
943877	NM_022436.3(ABCG5):c.635-153_1588del	Likely pathogenic

SpliceAI

2188 predictions. Top by Δscore:

Variant	Effect	Δscore
2:43776768:T:A	acceptor_gain	1.0000
2:43776777:T:G	acceptor_gain	1.0000
2:43776780:A:AG	acceptor_gain	1.0000
2:43776781:G:GA	acceptor_gain	1.0000
2:43776781:GT:G	acceptor_gain	1.0000
2:43776888:A:AG	donor_gain	1.0000
2:43776889:G:GG	donor_gain	1.0000
2:43776896:TGGGG:T	donor_loss	1.0000
2:43776897:GGG:G	donor_gain	1.0000
2:43776898:GGG:G	donor_gain	1.0000
2:43776899:GGTAA:G	donor_loss	1.0000
2:43776900:G:GA	donor_loss	1.0000
2:43776901:T:G	donor_loss	1.0000
2:43783511:A:AG	acceptor_gain	1.0000
2:43783512:A:G	acceptor_gain	1.0000
2:43783518:A:AG	acceptor_gain	1.0000
2:43783519:G:GG	acceptor_gain	1.0000
2:43783555:G:T	donor_loss	1.0000
2:43783556:T:G	donor_loss	1.0000
2:43789628:TTCAG:T	acceptor_loss	1.0000
2:43789629:TCAGC:T	acceptor_loss	1.0000
2:43789630:CA:C	acceptor_loss	1.0000
2:43789631:A:AG	acceptor_gain	1.0000
2:43789632:G:GA	acceptor_gain	1.0000
2:43789632:GC:G	acceptor_gain	1.0000
2:43789632:GCC:G	acceptor_gain	1.0000
2:43789632:GCCA:G	acceptor_gain	1.0000
2:43794456:GGAC:G	acceptor_gain	1.0000
2:43794480:T:TA	acceptor_gain	1.0000
2:43794481:G:A	acceptor_gain	1.0000

AlphaMissense

2324 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:43796761:G:C	R207P	0.996
2:43795936:G:A	G185E	0.995
2:43804704:T:A	W289R	0.995
2:43804704:T:C	W289R	0.995
2:43783527:C:T	T45I	0.994
2:43796758:T:C	L206P	0.994
2:43796785:C:A	A215E	0.993
2:43776885:G:C	G38R	0.992
2:43789646:C:A	A82D	0.992
2:43794504:T:C	L123P	0.992
2:43776886:G:A	G38D	0.991
2:43787229:A:C	R70S	0.991
2:43787229:A:T	R70S	0.991
2:43794486:T:C	L117P	0.991
2:43795938:A:C	S186R	0.991
2:43795940:T:A	S186R	0.991
2:43795940:T:G	S186R	0.991
2:43800901:T:C	F239L	0.991
2:43800903:T:A	F239L	0.991
2:43800903:T:G	F239L	0.991
2:43787207:C:A	A63D	0.990
2:43789654:T:A	W85R	0.990
2:43789654:T:C	W85R	0.990
2:43794471:T:A	V112D	0.990
2:43795930:T:A	I183K	0.990
2:43796769:G:C	A210P	0.990
2:43796784:G:C	A215P	0.990
2:43809709:T:C	L333P	0.990
2:43783520:G:A	G43R	0.989
2:43783520:G:C	G43R	0.989

dbSNP variants (sampled 300 via entrez): RS1000012088 (2:43828830 G>A), RS1000063837 (2:43793166 A>G), RS1000144214 (2:43788091 A>G,T), RS1000153962 (2:43788263 C>G), RS1000172177 (2:43774001 A>G), RS1000203263 (2:43774132 G>A), RS1000256589 (2:43798414 G>A,C,T), RS1000316499 (2:43810315 C>T), RS1000349274 (2:43783123 C>G,T), RS1000372087 (2:43818951 G>A), RS1000412756 (2:43778043 A>G,T), RS1000436422 (2:43792827 G>A,C,T), RS1000530861 (2:43773346 T>C), RS1000532803 (2:43807997 G>A), RS1000554858 (2:43808988 C>A)

Disease associations

OMIM: gene MIM:617083 | disease phenotypes: MIM:210250, MIM:215250, MIM:618666, MIM:617088, MIM:208500, MIM:263520

GenCC curated gene-disease

Disease	Classification	Inheritance
short-rib thoracic dysplasia 15 with polydactyly	Definitive	Autosomal recessive
Ellis-van Creveld syndrome	Supportive	Autosomal recessive
Jeune syndrome	Supportive	Autosomal recessive

Mondo (8): sitosterolemia (MONDO:0008863), sitosterolemia 1 (MONDO:0020747), sitosterolemia 2 (MONDO:0020748), short-rib thoracic dysplasia 15 with polydactyly (MONDO:0014907), asphyxiating thoracic dystrophy 1 (MONDO:0008831), short-rib thoracic dysplasia 6 with or without polydactyly (MONDO:0009894), Ellis-van Creveld syndrome (MONDO:0009162), Jeune syndrome (MONDO:0018770)

Orphanet (3): Sitosterolemia (Orphanet:2882), Jeune syndrome (Orphanet:474), Mediterranean macrothrombocytopenia (Orphanet:101022)

HPO phenotypes

96 total (30 of 96 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000039	Epispadias
HP:0000047	Hypospadias
HP:0000069	Abnormality of the ureter
HP:0000072	Hydroureter
HP:0000077	Abnormality of the kidney
HP:0000083	Renal insufficiency
HP:0000085	Horseshoe kidney
HP:0000090	Nephronophthisis
HP:0000112	Nephropathy
HP:0000148	Vaginal atresia
HP:0000161	Median cleft upper lip
HP:0000164	Abnormality of the dentition
HP:0000190	Abnormal oral frenulum morphology
HP:0000191	Accessory oral frenulum
HP:0000233	Thin vermilion border
HP:0000286	Epicanthus
HP:0000369	Low-set ears
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000668	Hypodontia
HP:0000684	Delayed eruption of teeth
HP:0000691	Microdontia
HP:0000766	Abnormal sternum morphology
HP:0000772	Abnormal rib morphology
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000888	Horizontal ribs

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST005196_201	Coronary artery disease	2.000000e-07
GCST006190_7	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	8.000000e-11
GCST006190_76	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-13
GCST006192_62	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-11
GCST006192_78	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-08
GCST006193_40	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-11
GCST006193_78	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-14
GCST006195_30	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-09
GCST006195_40	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	9.000000e-12
GCST90002383_167	Hematocrit	2.000000e-12
GCST90002384_46	Hemoglobin	7.000000e-12
GCST90002403_81	Red blood cell count	1.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004613	Ellis-Van Creveld Syndrome	C05.116.099.708.327; C16.131.077.350.398; C16.131.831.350.398; C16.320.850.250.398; C17.800.804.350.398; C17.800.827.250.398
C537571	Jeune syndrome (supp.)
C537345	Sitosterolemia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6720173	ABCG5, DYNC2LI1		0.00	0

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression	2
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Decitabine	affects expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Clorgyline	increases expression	1
Estradiol	affects expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	increases methylation	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Sodium Selenite	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

7 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)
NCT00004481	Not specified	COMPLETED	Genetic Study of Sitosterolemia
NCT00531128	Not specified	COMPLETED	The Effect of Dietary Sitosterol on Blood Sugar and Cholesterol
NCT01584206	Not specified	COMPLETED	Sitosterolemia Metabolism
NCT01948648	Not specified	UNKNOWN	Effects of Fish Oil and Colesevelam (STAIR7007)