NIN

Summary

NIN (ninein, HGNC:14906) is a protein-coding gene on chromosome 14q22.1, encoding Ninein (Q8N4C6). Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells.

This gene encodes one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the microtubules minus-ends in epithelial cells. Localization of this protein to the centrosome requires three leucine zippers in the central coiled-coil domain. Multiple alternatively spliced transcript variants that encode different isoforms have been reported.

Source: NCBI Gene 51199 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Seckel syndrome 7 (Limited, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 1,009 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 49
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_020921

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14906
Approved symbol	NIN
Name	ninein
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100503
Ensembl biotype	protein_coding
OMIM	608684
Entrez	51199

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 16 protein_coding, 12 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000324330, ENST00000382041, ENST00000382043, ENST00000389869, ENST00000453196, ENST00000453401, ENST00000463419, ENST00000474937, ENST00000476352, ENST00000480476, ENST00000485005, ENST00000486200, ENST00000486950, ENST00000496749, ENST00000530997, ENST00000555984, ENST00000673657, ENST00000673819, ENST00000673852, ENST00000674030, ENST00000674061, ENST00000706703, ENST00000706704, ENST00000706705, ENST00000706706, ENST00000706707, ENST00000706708, ENST00000706709, ENST00000706710, ENST00000706711, ENST00000706712, ENST00000872465, ENST00000914777, ENST00000965312

RefSeq mRNA: 4 — MANE Select: NM_020921 NM_016350, NM_020921, NM_182944, NM_182946

CCDS: CCDS32078, CCDS32079, CCDS45103, CCDS91876

Canonical transcript exons

ENST00000530997 — 31 exons

Exon	Start	End
ENSE00000657153	50766307	50766396
ENSE00000657154	50766780	50766890
ENSE00000657161	50772949	50773095
ENSE00000854679	50744243	50744365
ENSE00001093989	50735516	50735617
ENSE00001155177	50761790	50761911
ENSE00001155299	50754742	50754867
ENSE00001174786	50754563	50754632
ENSE00001184946	50759857	50760359
ENSE00001184989	50778765	50778804
ENSE00001245861	50747992	50748105
ENSE00001246122	50743416	50743529
ENSE00001246143	50752518	50752733
ENSE00001246158	50756492	50758630
ENSE00001246178	50763826	50763964
ENSE00001246198	50770388	50770562
ENSE00001322536	50739308	50739487
ENSE00001326635	50738140	50738286
ENSE00001357616	50770852	50770992
ENSE00001357619	50771332	50771468
ENSE00001357622	50772301	50772468
ENSE00001357628	50776949	50777139
ENSE00001774284	50830464	50830517
ENSE00003305744	50806737	50806818
ENSE00003539923	50729523	50729723
ENSE00003565427	50725953	50726066
ENSE00003600094	50792712	50792881
ENSE00003604887	50719763	50723672
ENSE00003667024	50821874	50822077
ENSE00003675294	50741582	50741728
ENSE00003901742	50831006	50831162

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 98.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.6075 / max 2022.9742, expressed in 1801 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143177	26.1339	1799
143176	0.9660	321
143173	0.6243	253
143175	0.3877	172
143174	0.2726	139
143178	0.2231	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	98.18	gold quality
buccal mucosa cell	CL:0002336	97.06	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.99	gold quality
tendon of biceps brachii	UBERON:0008188	94.73	gold quality
bone marrow cell	CL:0002092	94.70	gold quality
blood	UBERON:0000178	94.63	gold quality
sural nerve	UBERON:0015488	94.40	gold quality
monocyte	CL:0000576	94.37	gold quality
bone marrow	UBERON:0002371	94.16	gold quality
leukocyte	CL:0000738	94.15	gold quality
cortical plate	UBERON:0005343	94.11	gold quality
trabecular bone tissue	UBERON:0002483	93.66	gold quality
skin of hip	UBERON:0001554	92.29	gold quality
tendon	UBERON:0000043	92.14	gold quality
medial globus pallidus	UBERON:0002477	91.83	gold quality
adrenal tissue	UBERON:0018303	91.71	gold quality
left ventricle myocardium	UBERON:0006566	91.67	gold quality
upper arm skin	UBERON:0004263	91.61	gold quality
upper leg skin	UBERON:0004262	91.56	gold quality
corpus callosum	UBERON:0002336	91.45	gold quality
lymph node	UBERON:0000029	91.44	gold quality
superficial temporal artery	UBERON:0001614	91.09	gold quality
ileal mucosa	UBERON:0000331	91.05	gold quality
bronchial epithelial cell	CL:0002328	90.98	gold quality
placenta	UBERON:0001987	90.98	gold quality
tonsil	UBERON:0002372	90.85	gold quality
vermiform appendix	UBERON:0001154	90.73	gold quality
calcaneal tendon	UBERON:0003701	90.67	gold quality
tibialis anterior	UBERON:0001385	90.66	gold quality
colonic epithelium	UBERON:0000397	90.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.23
E-GEOD-93593	yes	8.21
E-GEOD-150728	no	757.45

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 20)

• Ninein is essential for the reformation of specific aspects of the interphase centrosome architecture following mitosis as well as being required for the centrosome to function as a MTOC. (PMID:11956314)
• ninein protein has two distinct subdomains required for centrosomal targeting and regulating signals in cell cycle (PMID:12927815)
• Elevated ninein causes mislocalization of gamma-tubulin, recruiting it to ectopic (noncentrosomal) ninein-containing sites which are not active in nucleating microtubules, suggesting a regulatory role for ninein in microtubule nucleation. (PMID:15190203)
• We propose that ninein constitutes a molecular link between microtubule-nucleation and -anchoring activities at the centrosome. (PMID:15784680)
• our findings place SUMOylation target on the centrosome structure protein, hNinein, which results in the switch localization from centrosome to nucleus (PMID:16154161)
• Overexpression of ninein and the ninein-like protein NIP induces fragmentation of the Golgi and causes lysosomes to disperse toward the cell periphery. (PMID:16254247)
• analysis of human ninein isoforms that are regulated by centrosomal targeting signals and bind to gamma-tubulin (PMID:17102634)
• hNinein regulates the dynamic movement of Astrin throughout the cell cycle and this interaction, in turn, is required for maintenance of centrosome/spindle pole integrity. (PMID:17383637)
• Data show that ninein is highly dynamic and that, in epithelial cells, it is present not only at the centrosome but also in the cytoplasm as distinct speckles. (PMID:17698918)
• Two single nucleotide polymorphisms in the APC and NIN loci were significantly associated with pancreatic cancer risk (PMID:20056645)
• Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein. (PMID:21325031)
• The prevalence of hNinein autoreactivity and its specificity in 22 rheumatoid arthritis and 32 systemic lupus erythematosus autoimmune disease sera. (PMID:21667027)
• Our analyses suggest a relationship with prenatal neurogenesis and identify the human data point as an outlier, possibly explained by postnatal changes in development on the human lineage. (PMID:22937743)
• The role of hNinein isoform 6 expression in cell differentiation was assessed in BrdU-treated IMR-32 cells (PMID:23047184)
• A Ninein (NIN) missense mutation identified in a family with spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type)-like phenotype. (PMID:23665482)
• JAK2 Tyrosine Kinase phosphorylates centrosomal protein ninein, which negatively regulates it (PMID:25332239)
• Ninein influences the rate of axonal growth and branching by affecting microtubule stability and dynamics. (PMID:25741725)
• Genetic susceptibility of common polymorphisms in NIN and SIGLEC5 to chronic periodontitis. (PMID:30765789)
• beta3-Endonexin interacts with ninein in vascular endothelial cells to promote angiogenesis. (PMID:34118594)
• Ninein promotes F-actin cup formation and inward phagosome movement during phagocytosis in macrophages. (PMID:38117588)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nin	ENSDARG00000060298
mus_musculus	Nin	ENSMUSG00000021068
rattus_norvegicus	Nin	ENSRNOG00000005540
drosophila_melanogaster	Nin	FBGN0000228
caenorhabditis_elegans		WBGENE00011444

Paralogs (1): NINL (ENSG00000101004)

Protein

Protein identifiers

Ninein — Q8N4C6 (reviewed: Q8N4C6)

Alternative names: Glycogen synthase kinase 3 beta-interacting protein

All UniProt accessions (14): Q8N4C6, A0A0B4J215, A0A669KBB6, A0A669KBE5, A0A669KBI5, A0A669KBK6, A0A9L9PXF3, A0A9L9PY96, C9J066, E9PJH9, E9PN67, H7C162, H9KV85, R4GN85

UniProt curated annotations — full annotation on UniProt →

Function. Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells. May also act as a centrosome maturation factor. May play a role in microtubule nucleation, by recruiting the gamma-tubulin ring complex to the centrosome. Overexpression does not perturb nucleation or elongation of microtubules but suppresses release of microtubules. Required for centriole organization and microtubule anchoring at the mother centriole.

Subunit / interactions. Homooligomer. Interacts with GSK3B/GSK3-beta via its C-terminal domain. Interacts with C14ORF166, such interaction may prevent its phosphorylation by GSK3B. Interacts with AUNIP (via N-terminus). Identified in a complex with AUNIP and AURKA. Interacts with CCDC120. Interacts (via C-terminus) with CEP250. Interacts with CEP170. Interacts with the gamma-tubulin ring complex component TUBGCP3. Interacts with gamma-tubulin. Interacts with DSP; the interaction facilitates recruitment of NIN to desmosome cell-cell junctions. Lacks interaction with CEP170 and CEP250.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cell junction. Desmosome Cytoplasm.

Tissue specificity. Ubiquitous. Highly expressed in heart and skeletal muscle. Isoform 1 is more expressed than isoform 5.

Post-translational modifications. Phosphorylated by AURKA/Aurora kinase A and PKA kinases but not CK2 or AURKB/ Aurora kinase B.

Disease relevance. Seckel syndrome 7 (SCKL7) [MIM:614851] A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. There is conflicting information regarding the regions required for centrosomal localization. One study shows that the region 1601-1682 is necessary and sufficient for targeting to the centrosome. Another study shows that a separate region, 1291-1575, is important for centrosomal localization. However, a third study shows that the coiled-coil region (373-1885) is not sufficient for centrosomal localization and instead localizes to cytoplasmic speckles. The observed differences might be due to oligomerization of the longer coiled-coil domain-containing sequence, which would mask the shorter centrosomal targeting sequences. The N-terminal domain is important for targeting to the mother centriole, although it is not sufficient by itself for centrosomal localization.

Miscellaneous. Antibodies against NIN are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins. Dubious isoform produced through aberrant splice sites. Dubious isoform produced through aberrant splice sites. Dubious isoform produced through aberrant splice sites.

Isoforms (9)

UniProt ID	Names	Canonical?
Q8N4C6-1	1, Lm	yes
Q8N4C6-2	2, Isotype 3
Q8N4C6-10	3, Isotype 2
Q8N4C6-4	4, Isotype 1
Q8N4C6-5	5
Q8N4C6-6	6
Q8N4C6-7	7, B
Q8N4C6-9	8
Q8N4C6-11	9

RefSeq proteins (4): NP_057434, NP_065972, NP_891989, NP_891991 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily

UniProt features (59 total): sequence conflict 18, splice variant 10, coiled-coil region 7, sequence variant 7, domain 5, modified residue 4, region of interest 4, binding site 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4C6-F1	64.47	0.04

Functional residue map

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

Ligand- & substrate-binding residues (3): 245–252; 300–304; 420–423

Post-translational modifications (4): 152, 269, 1550, 1837

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 413 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_MICROTUBULE_ANCHORING, CHUNG_BLISTER_CYTOTOXICITY_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GEORGES_CELL_CYCLE_MIR192_TARGETS, GOBP_GROWTH, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_MICROTUBULE_NUCLEATION, GGGTGGRR_PAX4_03, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (9): intracellular protein localization (GO:0008104), centriole-centriole cohesion (GO:0010457), corpus callosum morphogenesis (GO:0021540), corticospinal tract morphogenesis (GO:0021957), microtubule anchoring at centrosome (GO:0034454), collateral sprouting (GO:0048668), positive regulation of axonogenesis (GO:0050772), centrosome localization (GO:0051642), centrosome-templated microtubule nucleation (GO:0090222)

GO Molecular Function (5): calcium ion binding (GO:0005509), GTP binding (GO:0005525), microtubule minus-end binding (GO:0051011), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (21): pericentriolar material (GO:0000242), spindle pole (GO:0000922), nucleoplasm (GO:0005654), nucleolus (GO:0005730), centrosome (GO:0005813), centriole (GO:0005814), cytoplasmic microtubule (GO:0005881), plasma membrane (GO:0005886), dendrite (GO:0030425), ciliary basal body (GO:0036064), axonal growth cone (GO:0044295), apical part of cell (GO:0045177), mitotic spindle (GO:0072686), mitotic spindle pole (GO:0097431), ciliary transition fiber (GO:0097539), centriolar subdistal appendage (GO:0120103), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), microtubule (GO:0005874), axon (GO:0030424)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
intracellular membraneless organelle	3
microtubule organizing center	3
cilium	3
central nervous system projection neuron axonogenesis	2
axonogenesis	2
spindle	2
nuclear lumen	2
intracellular protein-containing complex	2
microtubule cytoskeleton	2
macromolecule localization	1
centrosome cycle	1
cell cycle process	1
corpus callosum development	1
microtubule anchoring at microtubule organizing center	1
developmental cell growth	1
developmental growth involved in morphogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
microtubule organizing center localization	1
microtubule nucleation by microtubule organizing center	1
metal ion binding	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
microtubule binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
centrosome	1
centriole	1
cytoplasm	1
microtubule	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
growth cone	1
spindle pole	1
mitotic spindle	1

Protein interactions and networks

STRING

1960 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NIN	PCNT	O95613	976
NIN	CNTRL	Q7Z7A1	962
NIN	RTRAF	Q9Y224	907
NIN	CEP250	Q9BV73	901
NIN	CNTLN	Q9NXG0	898
NIN	CNTROB	Q8N137	886
NIN	ODF2	Q5BJF6	879
NIN	CEP170	Q5SW79	878
NIN	SDCCAG8	Q86SQ7	864
NIN	PCM1	Q15154	854
NIN	CETN1	Q12798	844
NIN	CEP128	Q6ZU80	826
NIN	TUBE1	Q9UJT0	788
NIN	CCDC120	Q96HB5	785
NIN	CEP164	Q9UPV0	774

IntAct

99 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CCDC120	CEP170	psi-mi:“MI:0914”(association)	0.820
CCDC120	NIN	psi-mi:“MI:0403”(colocalization)	0.680
NIN	CCDC120	psi-mi:“MI:0915”(physical association)	0.680
NIN	CCDC120	psi-mi:“MI:0407”(direct interaction)	0.680
CCDC120	NIN	psi-mi:“MI:0915”(physical association)	0.680
NIN	CCDC120	psi-mi:“MI:0403”(colocalization)	0.680
NIN	GSK3B	psi-mi:“MI:0915”(physical association)	0.670
NIN	GSK3B	psi-mi:“MI:0217”(phosphorylation reaction)	0.670
NIN	GSK3B	psi-mi:“MI:0403”(colocalization)	0.670
CCDC68	NDC80	psi-mi:“MI:0914”(association)	0.640
CCDC120	ODF2	psi-mi:“MI:0403”(colocalization)	0.600
NIN	RTRAF	psi-mi:“MI:0915”(physical association)	0.560
RTRAF	NIN	psi-mi:“MI:0915”(physical association)	0.560
NIN	RTRAF	psi-mi:“MI:0407”(direct interaction)	0.560
RTRAF	NIN	psi-mi:“MI:0403”(colocalization)	0.560
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
CCT6A	TXNDC9	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
PPP1R13B	CCDC85C	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
CASQ2	PES1	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
COG5	BSG	psi-mi:“MI:0914”(association)	0.530

BioGRID (466): NIN (Affinity Capture-MS), NIN (Affinity Capture-MS), NIN (Affinity Capture-MS), NIN (Affinity Capture-MS), NIN (Affinity Capture-MS), NIN (Proximity Label-MS), NIN (Proximity Label-MS), NIN (Affinity Capture-MS), NIN (Proximity Label-MS), NIN (Proximity Label-MS), NIN (Proximity Label-MS), ACTR1A (Proximity Label-MS), ANLN (Proximity Label-MS), AP3D1 (Proximity Label-MS), CEP131 (Proximity Label-MS)

ESM2 similar proteins: A0JMQ7, A0JMY4, A2AUM9, A2BDR7, A2BGP7, A6NI79, A6PWD2, A6QNP9, B1AJZ9, D3YV10, G9G127, O35550, O35551, O75330, O94986, P0CB05, Q05D60, Q0VFN8, Q0VFX2, Q15276, Q17QT2, Q3UPP8, Q498G2, Q4KLY0, Q4PJT6, Q4R703, Q4V7B0, Q5JU67, Q5NVN6, Q5U3A8, Q5U3Z6, Q5U4W1, Q5ZL12, Q66KE8, Q6DFC2, Q6DIS8, Q6IMY1, Q6NRC9, Q6P402, Q7M6Y5

Diamond homologs: G9G127, Q61043, Q6ZQ12, Q8N4C6, Q9Y2I6, Q8IZ41

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NIN	down-regulates	JAK2	binding
PCM1	up-regulates	NIN	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
Loss of Nlp from mitotic centrosomes	13	24.0×	1e-12
Loss of proteins required for interphase microtubule organization from the centrosome	13	24.0×	1e-12
AURKA Activation by TPX2	13	23.0×	1e-12
Recruitment of mitotic centrosome proteins and complexes	13	20.6×	4e-12
Regulation of PLK1 Activity at G2/M Transition	13	19.2×	8e-12
Recruitment of NuMA to mitotic centrosomes	14	19.0×	1e-12
Centrosome maturation	6	17.7×	5e-05
Anchoring of the basal body to the plasma membrane	13	17.1×	3e-11

GO biological processes:

GO term	Partners	Fold	FDR
microtubule bundle formation	5	21.6×	5e-04
mitotic spindle organization	6	13.8×	6e-04
microtubule cytoskeleton organization	9	9.2×	2e-04
intracellular protein localization	9	8.0×	5e-04
cilium assembly	9	5.6×	3e-03
cell division	12	4.7×	1e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — COADREAD, PLMESO, STAD.

Clinical variants and AI predictions

ClinVar

1009 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	595
Likely benign	246
Benign	97

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
211602	NM_020921.4(NIN):c.2482del (p.Arg828fs)	Pathogenic
4525807	NM_020921.4(NIN):c.4100_4103del (p.Asn1367fs)	Pathogenic
689178	GRCh37/hg19 14q22.1(chr14:51152773-51216251)x1	Pathogenic
4845858	NM_020921.4(NIN):c.2290C>T (p.Gln764Ter)	Likely pathogenic
804469	NM_020921.4(NIN):c.6115C>T (p.Arg2039Ter)	Likely pathogenic
930474	NM_020921.4(NIN):c.6079-1686G>A	Likely pathogenic

SpliceAI

4444 predictions. Top by Δscore:

Variant	Effect	Δscore
14:50726065:CC:C	acceptor_gain	1.0000
14:50726066:CC:C	acceptor_gain	1.0000
14:50726067:C:CC	acceptor_gain	1.0000
14:50727582:A:AC	donor_gain	1.0000
14:50727582:AATT:A	donor_gain	1.0000
14:50727583:A:C	donor_gain	1.0000
14:50727599:G:C	donor_gain	1.0000
14:50729519:ATAC:A	donor_loss	1.0000
14:50729521:A:AC	donor_gain	1.0000
14:50729522:C:CC	donor_gain	1.0000
14:50729522:C:CT	donor_loss	1.0000
14:50735511:CTTAC:C	donor_loss	1.0000
14:50735512:TTAC:T	donor_loss	1.0000
14:50735513:TACCT:T	donor_loss	1.0000
14:50735514:A:AC	donor_gain	1.0000
14:50735514:A:T	donor_loss	1.0000
14:50735514:ACCT:A	donor_gain	1.0000
14:50735514:ACCTC:A	donor_gain	1.0000
14:50735515:C:CG	donor_gain	1.0000
14:50735515:CCT:C	donor_gain	1.0000
14:50735515:CCTC:C	donor_gain	1.0000
14:50735515:CCTCC:C	donor_gain	1.0000
14:50735613:CTGAC:C	acceptor_gain	1.0000
14:50735614:TGAC:T	acceptor_gain	1.0000
14:50735615:GAC:G	acceptor_gain	1.0000
14:50735615:GACCT:G	acceptor_loss	1.0000
14:50735616:ACCTG:A	acceptor_loss	1.0000
14:50735618:C:CC	acceptor_gain	1.0000
14:50735618:C:T	acceptor_loss	1.0000
14:50735622:T:C	acceptor_gain	1.0000

AlphaMissense

14212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:50806802:A:G	F67S	0.999
14:50772342:A:G	W314R	0.998
14:50772342:A:T	W314R	0.998
14:50792830:C:T	G106E	0.998
14:50806798:T:A	K68N	0.998
14:50806798:T:G	K68N	0.998
14:50821950:A:G	L36P	0.998
14:50821959:A:G	L33P	0.998
14:50822019:A:G	L13P	0.998
14:50806794:C:G	A70P	0.997
14:50821938:A:G	L40S	0.997
14:50822019:A:T	L13H	0.997
14:50770886:C:G	A409P	0.996
14:50806810:A:C	F64L	0.996
14:50806810:A:T	F64L	0.996
14:50806812:A:G	F64L	0.996
14:50822006:A:C	F17L	0.996
14:50822006:A:T	F17L	0.996
14:50822008:A:G	F17L	0.996
14:50726005:A:G	L2047P	0.995
14:50792834:A:G	Y105H	0.995
14:50806790:A:G	L71S	0.995
14:50806801:A:C	F67L	0.995
14:50806801:A:T	F67L	0.995
14:50806803:A:G	F67L	0.995
14:50821959:A:T	L33H	0.995
14:50822010:A:G	L16P	0.995
14:50770910:C:G	A401P	0.994
14:50770942:A:G	L390P	0.994
14:50792823:C:A	R108S	0.994

dbSNP variants (sampled 300 via entrez): RS1000019829 (14:50788125 C>T), RS1000051897 (14:50729271 AT>A,ATTTTTTTTTTTTTTTTTTTTTTT), RS1000078883 (14:50781487 T>C,G), RS1000103090 (14:50820564 C>T), RS1000121254 (14:50721235 G>C), RS1000134575 (14:50781952 T>G), RS1000146616 (14:50778666 T>C), RS1000162969 (14:50760478 T>C), RS1000178192 (14:50724994 G>C), RS1000184981 (14:50804628 C>T), RS1000223728 (14:50808669 G>T), RS1000257171 (14:50804961 T>C), RS1000269583 (14:50778388 G>T), RS1000275513 (14:50771822 C>A), RS1000295902 (14:50773897 G>A)

Disease associations

OMIM: gene MIM:608684 | disease phenotypes: MIM:614851, MIM:210600, MIM:608629

GenCC curated gene-disease

Disease	Classification	Inheritance
Seckel syndrome 7	Limited	Autosomal recessive

Mondo (3): Seckel syndrome 7 (MONDO:0013922), Seckel syndrome (MONDO:0019342), Joubert syndrome 3 (MONDO:0012078)

Orphanet (4): Microcephalic primordial dwarfism, Dauber type (Orphanet:319675), Microcephalic primordial dwarfism (Orphanet:324761), Seckel syndrome (Orphanet:808), Joubert syndrome with ocular defect (Orphanet:220493)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000387	Absent earlobe
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000601	Hypotelorism
HP:0000682	Abnormal dental enamel morphology
HP:0000786	Primary amenorrhea
HP:0001191	Abnormal carpal morphology
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001511	Intrauterine growth retardation
HP:0001513	Obesity
HP:0001607	Subglottic stenosis
HP:0001852	Sandal gap
HP:0002209	Sparse scalp hair
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0003067	Madelung deformity
HP:0003510	Severe short stature

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000579_7	Cognitive performance	5.000000e-07
GCST002312_10	Periodontal disease-related phenotype (Socransky)	8.000000e-06
GCST002479_13	Lupus nephritis in systemic lupus erythematosus	3.000000e-07
GCST004599_163	Mean platelet volume	2.000000e-11
GCST007270_7	Systolic blood pressure	4.000000e-18
GCST007271_3	Diastolic blood pressure	4.000000e-13
GCST007272_11	Pulse pressure	1.000000e-09
GCST009238_3	Asthma (time to childhood onset) x early life tobacco smoke interaction	3.000000e-06
GCST010002_150	Refractive error	1.000000e-11
GCST011176_7	Stroke	3.000000e-07
GCST011769_6	Schizophrenia	2.000000e-08
GCST012204_1	Rectal cancer	5.000000e-09
GCST90011898_24	Alanine aminotransferase levels	6.000000e-12
GCST90013663_55	Alanine aminotransferase levels	3.000000e-14
GCST90013664_55	Aspartate aminotransferase levels	4.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004847	age at onset
EFO:0008361	environmental tobacco smoke exposure measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536295	Joubert syndrome 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

1 measured of 2 human assays (3 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
NSC 705701	IC50	35 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	7
Acetaminophen	affects expression, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
trichostatin A	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance, increases oxidation	2
aristolochic acid I	decreases expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
sodium arsenite	increases expression	1
alpha-cobratoxin	decreases reaction, increases expression, decreases expression	1
methacrylaldehyde	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
lei gong teng	increases expression	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
N-butyrylglucosamine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	affects response to substance	1
Sunitinib	increases expression	1
Cidofovir	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03139903	Not specified	COMPLETED	The Primordial Dwarfisms: Diagnosis, Identification of the Molecular Basis of Seckel Syndrome and Microcephalic Osteodysplastic Primordial Dwarfism Type II