NUDCD3

Summary

NUDCD3 (NudC domain containing 3, HGNC:22208) is a protein-coding gene on chromosome 7p13, encoding NudC domain-containing protein 3 (Q8IVD9). It is a selective cancer dependency (DepMap: 60.8% of cell lines).

The product of this gene functions to maintain the stability of dynein intermediate chain. Depletion of this gene product results in aggregation and degradation of dynein intermediate chain, mislocalization of the dynein complex from kinetochores, spindle microtubules, and spindle poles, and loss of gamma-tubulin from spindle poles. The protein localizes to the Golgi apparatus during interphase, and levels of the protein increase after the G1/S transition.

Source: NCBI Gene 23386 — RefSeq curated summary.

At a glance

• Gene–disease (curated): severe combined immunodeficiency (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 56 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 47 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 28
• Cancer dependency (DepMap): dependent in 60.8% of screened cell lines
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.49 (moderately constrained)
• MANE Select transcript: NM_015332

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22208
Approved symbol	NUDCD3
Name	NudC domain containing 3
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1068, NudCL
Ensembl gene	ENSG00000015676
Ensembl biotype	protein_coding
OMIM	610296
Entrez	23386

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 9 protein_coding, 8 protein_coding_CDS_not_defined, 7 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000355451

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 5, TSL 4: 2, TSL 5: 1

ENST00000355451, ENST00000338427, ENST00000460110, ENST00000464812, ENST00000472246, ENST00000475952, ENST00000478769, ENST00000480209, ENST00000487118, ENST00000493613, ENST00000497978, ENST00000873878, ENST00000873879, ENST00000962334, ENST00001004564, ENST00001004565, ENST00001004566, ENST00001026140, ENST00001083917, ENST00001083918, ENST00001109720, ENST00001109721, ENST00001109722, ENST00001115740, ENST00001128864, ENST00001141902

RefSeq mRNA: 1 — MANE Select: NM_015332 NM_015332

CCDS: CCDS5490

Canonical transcript exons

ENST00000355451 — 6 exons

Exon	Start	End
ENSE00001551580	44379119	44386121
ENSE00001700145	44490409	44490658
ENSE00003554652	44484968	44485284
ENSE00003650008	44427571	44427703
ENSE00003655068	44404440	44404583
ENSE00003676277	44392297	44392485

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.9815 / max 559.7910, expressed in 1821 samples.

Highest expression (Bgee): cortical plate, prefrontal cortex, frontal lobe, Brodmann (1909) area 9, cerebellar hemisphere.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NUDCD3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 47 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 49 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	3.7e-82	+0.84	7:44436151:C:T
Nerve Tibial	eqtl	2.8e-78	+0.65	7:44436151:C:T
Adipose Subcutaneous	eqtl	2.7e-59	+0.52	7:44382475:A:G
Esophagus Muscularis	eqtl	1.7e-58	+0.48	7:44490127:G:A
Artery Tibial	eqtl	3.2e-56	+0.41	7:44426572:G:A
Skin Sun Exposed Lower leg	eqtl	5.2e-44	+0.32	7:44490127:G:A
Breast Mammary Tissue	eqtl	1.3e-43	+0.56	7:44364244:G:T
Colon Sigmoid	eqtl	4.5e-41	+0.43	7:44363508:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-40	+0.37	7:44373902:T:C
Esophagus Gastroesophageal Junction	eqtl	5.2e-40	+0.49	7:44368369:A:G
Lung	eqtl	2.4e-34	+0.36	7:44492295:C:G
Artery Aorta	eqtl	1.5e-32	+0.49	7:44490127:G:A
Colon Transverse	eqtl	3.9e-30	+0.35	7:44368369:A:G
Adipose Visceral Omentum	eqtl	6.8e-30	+0.50	7:44382475:A:G
Cells Cultured fibroblasts	eqtl	8.0e-28	+0.33	7:44373902:T:C
Whole Blood	eqtl	1.0e-27	+0.27	7:44373902:T:C
Esophagus Mucosa	eqtl	8.8e-27	+0.36	7:44490127:G:A
Pituitary	eqtl	1.3e-26	+0.63	7:44503570:G:A
Spleen	eqtl	3.1e-25	+0.69	7:44368369:A:G
Prostate	eqtl	3.2e-25	+0.62	7:44426572:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
83875	33.9815	1821

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.17	gold quality
prefrontal cortex	UBERON:0000451	97.10	gold quality
right frontal lobe	UBERON:0002810	96.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.51	gold quality
cerebellar hemisphere	UBERON:0002245	96.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.43	gold quality
cerebellar cortex	UBERON:0002129	96.37	gold quality
gastrocnemius	UBERON:0001388	96.27	gold quality
muscle of leg	UBERON:0001383	96.23	gold quality
stromal cell of endometrium	CL:0002255	96.09	gold quality
nucleus accumbens	UBERON:0001882	95.99	gold quality
cerebellum	UBERON:0002037	95.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.54	gold quality
islet of Langerhans	UBERON:0000006	95.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.25	gold quality
sural nerve	UBERON:0015488	95.25	gold quality
popliteal artery	UBERON:0002250	95.16	gold quality
tibial artery	UBERON:0007610	95.15	gold quality
putamen	UBERON:0001874	95.09	gold quality
caudate nucleus	UBERON:0001873	95.07	gold quality
primary visual cortex	UBERON:0002436	95.06	gold quality
ganglionic eminence	UBERON:0004023	95.01	gold quality
frontal cortex	UBERON:0001870	94.98	gold quality
middle temporal gyrus	UBERON:0002771	94.95	gold quality
aorta	UBERON:0000947	94.94	gold quality
occipital lobe	UBERON:0002021	94.94	gold quality
neocortex	UBERON:0001950	94.86	gold quality
descending thoracic aorta	UBERON:0002345	94.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.75	gold quality
lower esophagus	UBERON:0013473	94.74	gold quality
telencephalon	UBERON:0001893	94.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.69	gold quality
thoracic aorta	UBERON:0001515	94.68	gold quality
ascending aorta	UBERON:0001496	94.64	gold quality
cerebral cortex	UBERON:0000956	94.62	gold quality
body of uterus	UBERON:0009853	94.59	gold quality
right coronary artery	UBERON:0001625	94.58	gold quality
gall bladder	UBERON:0002110	94.57	gold quality
brain	UBERON:0000955	94.52	gold quality
central nervous system	UBERON:0001017	94.46	gold quality
forebrain	UBERON:0001890	94.46	gold quality
hypothalamus	UBERON:0001898	94.37	gold quality
cingulate cortex	UBERON:0003027	94.31	gold quality
tendon of biceps brachii	UBERON:0008188	94.30	gold quality
muscle organ	UBERON:0001630	94.28	gold quality
esophagus	UBERON:0001043	94.24	gold quality
amygdala	UBERON:0001876	94.21	gold quality
pons	UBERON:0000988	94.16	gold quality
left uterine tube	UBERON:0001303	94.16	gold quality
parietal lobe	UBERON:0001872	94.15	gold quality
superior frontal gyrus	UBERON:0002661	94.14	gold quality
anterior cingulate cortex	UBERON:0009835	94.14	gold quality
left testis	UBERON:0004533	94.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.10	gold quality
left ovary	UBERON:0002119	94.09	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.09	gold quality
right uterine tube	UBERON:0001302	94.08	gold quality
lower esophagus mucosa	UBERON:0035834	93.99	gold quality
endocervix	UBERON:0000458	93.98	gold quality
right adrenal gland cortex	UBERON:0035827	93.97	gold quality
coronary artery	UBERON:0001621	93.93	gold quality
right ovary	UBERON:0002118	93.93	gold quality
right testis	UBERON:0004534	93.91	gold quality
apex of heart	UBERON:0002098	93.90	gold quality
left coronary artery	UBERON:0001626	93.86	gold quality
ventricular zone	UBERON:0003053	93.86	gold quality
ectocervix	UBERON:0012249	93.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.81	gold quality
superior vestibular nucleus	UBERON:0007227	93.80	gold quality
left adrenal gland	UBERON:0001234	93.76	gold quality
temporal lobe	UBERON:0001871	93.76	gold quality
esophagus mucosa	UBERON:0002469	93.76	gold quality
postcentral gyrus	UBERON:0002581	93.74	gold quality
pancreatic ductal cell	CL:0002079	93.71	gold quality
Ammon’s horn	UBERON:0001954	93.71	gold quality
lateral globus pallidus	UBERON:0002476	93.69	gold quality
skin of leg	UBERON:0001511	93.68	gold quality
substantia nigra pars compacta	UBERON:0001965	93.66	gold quality
ovary	UBERON:0000992	93.65	gold quality
vagina	UBERON:0000996	93.64	gold quality
right adrenal gland	UBERON:0001233	93.64	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.62	gold quality
calcaneal tendon	UBERON:0003701	93.62	gold quality
right atrium auricular region	UBERON:0006631	93.59	gold quality
ventral tegmental area	UBERON:0002691	93.54	gold quality
smooth muscle tissue	UBERON:0001135	93.51	gold quality
adrenal gland	UBERON:0002369	93.51	gold quality
left adrenal gland cortex	UBERON:0035825	93.50	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.48	gold quality
adrenal cortex	UBERON:0001235	93.47	gold quality
endothelial cell	CL:0000115	93.46	gold quality
mucosa of stomach	UBERON:0001199	93.46	gold quality
tonsil	UBERON:0002372	93.42	gold quality
medial globus pallidus	UBERON:0002477	93.41	gold quality
globus pallidus	UBERON:0001875	93.34	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.32	gold quality
heart left ventricle	UBERON:0002084	93.31	gold quality
rectum	UBERON:0001052	93.30	gold quality
midbrain	UBERON:0001891	93.17	gold quality
substantia nigra	UBERON:0002038	93.12	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-110499	no	411.49
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	48.8
Caudate putamen	tissue	44.6
Cerebral cortex	tissue	31.5	high
Somatosensory cortex	tissue	31.5
Putamen	tissue	29.4
Motor cortex	tissue	28.8
Occipital cortex	tissue	27.8
Prefrontal cortex	tissue	26.8
Basal ganglia	tissue	26.6	medium
Nucleus accumbens	tissue	26.4
Temporal cortex	tissue	25.2
Hippocampal formation	tissue	25.0
Entorhinal cortex	tissue	25.0
Retrosplenial and cingulate cortex	tissue	24.8
Pons	tissue	24.6
Insular cortex	tissue	24.5
Thalamus	tissue	23.9
Retrosplenial cortex	tissue	23.9
Superior colliculi	tissue	23.3
Midbrain	tissue	22.7
Locus coeruleus	tissue	22.1
Postcentral gyrus	tissue	22.0
Cerebellum	tissue	21.9	high
Hippocampus	tissue	21.9	medium
Ventral forebrain	tissue	21.7
Hypothalamus	tissue	21.3
Medulla oblongata	tissue	21.0
Substantia nigra	tissue	20.3
Spinal cord	tissue	19.8
Amygdala	tissue	19.0
Olfactory bulb	tissue	18.6
Periaqueductal gray	tissue	18.5
Septum	tissue	18.5
Corpus callosum	tissue	17.0
Choroid plexus	tissue	9.1
Skeletal muscle	tissue	7.2	medium
Heart muscle	tissue	7.1	medium
Tongue	tissue	5.3
Retina	tissue	4.4
Parathyroid gland	tissue	3.5	high
Fallopian tube	tissue	3.3	medium
Seminal vesicle	tissue	3.1	low
Testis	tissue	2.9	high
Smooth muscle	tissue	2.8	high
Adipose tissue	tissue	2.7	medium
Ovary	tissue	2.6	medium
Esophagus	tissue	2.6	medium
Thyroid gland	tissue	2.6	medium
Prostate	tissue	2.6	medium
Bone marrow	tissue	2.6	low
Cervix	tissue	2.3	high
Salivary gland	tissue	2.3	medium
Lung	tissue	2.3	medium
Skin 1	tissue	2.2	medium
Breast	tissue	2.2	medium
Epididymis	tissue	2.2	medium
Lymph node	tissue	2.1	medium
Pancreas	tissue	2.1	low
Endometrium 1	tissue	2.1	medium
Tonsil	tissue	2.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Caudate nucleus (27.4), Nucleus basalis of Meynert (25.0), Claustrum (24.8), Parieto-insular cortex (24.4), Supramarginal gyrus (24.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting NUDCD3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 82 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-2392	99.43	67.50	708

Functional genomics

gnomAD constraint: pLI 0.987, LOEUF 0.492, missense Z 0.35 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000355451 — one region, missense o/e 0.99. DepMap (CRISPR cell-line fitness): dependent in 60.8% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): D283 Med (-1.47), C32 (-1.155), Capan-1 (-1.136), EFM-19 (-1.133), Caov-4 (-1.128), PEER (-1.026), MV4-11 (-1.022), HCC1419 (-1.021), NCI-H1944 (-1.015), KP-N-SI9s (-1.013), LS513 (-1.001), M-07e (-0.996), KMS-27 (-0.993), RL (-0.982), RT4 (-0.965).

Literature-anchored findings (GeneRIF, showing 2)

• Data characterize a previously undescribed mammalian NudC-like protein (NudCL), which appears to influence the stabilization of dynein intermediate chain (PMID:16754861)
• overexpression of NudCL inhibits cytokinesis (PMID:19806165)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nudcd3	ENSDARG00000098361
mus_musculus	Nudcd3	ENSMUSG00000053838
rattus_norvegicus	Nudcd3	ENSRNOG00000056148
drosophila_melanogaster	CG31251	FBGN0051251

Paralogs (2): NUDC (ENSG00000090273), NUDCD2 (ENSG00000170584)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2144158) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	1
decreased body size	1
thymus hypoplasia	1
infertility	1
increased circulating insulin level	1
abnormal T cell differentiation	1
abnormal bone marrow cell morphology/development	1
increased IgM level	1
increased IgE level	1
increased pre-B cell number	1
increased double-negative T cell number	1
increased double-positive T cell number	1
increased circulating creatinine level	1
decreased circulating glucose level	1
increased blood urea nitrogen level	1
decreased NK T cell number	1
increased memory T cell number	1
increased IgG2b level	1
abnormal T cell receptor V(D)J recombination	1
abnormal immunoglobulin light chain V-J recombination	1
increased red blood cell distribution width	1
increased DN3 thymocyte number	1
prenatal lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RB75	98.6%	Diamond
Gallus gallus	Q5ZIN1	81.6%	Diamond
Aspergillus nidulans FGSC A4	P17624	54.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
NPC1L1	protein-coding	29881
DDX56	protein-coding	54606
CAMK2B	protein-coding	816
GCK	protein-coding	2645
YKT6	protein-coding	10652

Protein

Protein identifiers

NudC domain-containing protein 3 — Q8IVD9 (reviewed: Q8IVD9)

All UniProt accessions (1): Q8IVD9

RefSeq proteins (1): NP_056147* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007052	CS_dom	Domain
IPR008978	HSP20-like_chaperone	Homologous_superfamily
IPR025934	NudC_N_dom	Domain
IPR037898	NudC_fam	Family
IPR037905	p23_NUDCD3	Domain

Pfam: PF04969, PF14050

UniProt features (23 total): strand 9, modified residue 3, sequence variant 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, helix 1, turn 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
1WGV	Solution Structure of the CS Domain of Human KIAA1068 Protein	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVD9-F1	80.39	0.50

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane; primary cilium; primary cilium tip; principal piece

Antibody reliability (HPA): IH enhanced · IF approved

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 (3)

Type	Positions
Phosphoserine	146, 340, 355

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 138 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_PROTEIN_MATURATION, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_PROTEIN_FOLDING, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, chr7p13, GOBP_CELL_PROJECTION_ORGANIZATION, HAN_SATB1_TARGETS_DN, ZHENG_BOUND_BY_FOXP3, ZHENG_FOXP3_TARGETS_IN_THYMUS_UP, GOCC_CYTOPLASMIC_DYNEIN_COMPLEX

GO Biological Process (3): protein folding (GO:0006457), cilium assembly (GO:0060271), protein localization to pericentriolar material (GO:1905793)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), cytoplasmic dynein complex (GO:0005868)

GO top-level categories

15 GO namespaces:

Category	Terms
cellular process	1
protein maturation	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 localization to centrosome	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
dynein complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 7 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
cilium assembly	BP	mutant phenotype
protein localization to pericentriolar material	BP	mutant phenotype
cytoplasmic dynein complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 890 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUDCD3	DYNC1H1	Q14204	781
NUDCD3	PTGES3	Q15185	775
NUDCD3	DYNC1I1	O14576	754
NUDCD3	NUDCD2	Q8WVJ2	654
NUDCD3	TUBG1	P23258	604
NUDCD3	PPP1R35	Q8TAP8	513
NUDCD3	NUDCD1	Q96RS6	500
NUDCD3	UBFD1	O14562	476
NUDCD3	NAGPA	Q9UK23	469
NUDCD3	ZMIZ2	Q8NF64	459
NUDCD3	INTS15	Q96N11	459
NUDCD3	TMEM68	Q96MH6	459
NUDCD3	PHF20L1	A8MW92	456
NUDCD3	PIGT	Q969N2	440
NUDCD3	MEA1	Q16626	439

IntAct

Human interaction partners of NUDCD3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 101 partners by confidence:

Partner	Interaction type	MIscore	Records
GAN	physical association	0.740	1
KLHDC2	physical association	0.740	1
KLHL22	physical association	0.740	1
KLHL6	association	0.670	2
HCFC2	physical association	0.670	1
KLHDC8A	physical association	0.670	1
KLHL15	physical association	0.670	1
KLHL29	physical association	0.670	1
KLHL23	physical association	0.640	2
KLHDC10	physical association	0.560	1
KLHL1	physical association	0.560	1
KLHL26	physical association	0.560	1
PAFAH1B1	physical association	0.520	2
KLHL38	physical association	0.500	1
RADX	physical association	0.500	1
SF3B3	physical association	0.500	1
HCFC1	physical association	0.400	2
AAAS	physical association	0.400	1
BAG2	physical association	0.400	1
BBS1	physical association	0.400	1
C20orf194	physical association	0.400	1
CALCR	physical association	0.400	1
CDK10	physical association	0.400	1
CFAP52	physical association	0.400	1
CFLAR	physical association	0.400	1
CHLR1	physical association	0.400	1
CLCN2	physical association	0.400	1
CRAT	physical association	0.400	1
CTCFL	physical association	0.400	1
DDB1	physical association	0.400	1

BioGRID (214 interactions; top human partners by supporting records): FKBP5 (Affinity Capture-MS; 7 records), CUL3 (Affinity Capture-MS; 4 records), KBTBD4 (Affinity Capture-MS; 4 records), KLHL20 (Affinity Capture-MS; 4 records), KLHDC3 (Affinity Capture-MS; 3 records), KLHL14 (Affinity Capture-MS; 3 records), KLHL18 (Affinity Capture-MS; 3 records), KLHL6 (Affinity Capture-MS; 3 records), KLHL9 (Affinity Capture-MS; 3 records), AKAP1 (Proximity Label-MS; 2 records), CARM1 (Affinity Capture-Luminescence; 2 records), CXorf57 (Affinity Capture-Luminescence; 2 records), ENC1 (Affinity Capture-MS; 2 records), FAM136A (Affinity Capture-Luminescence; 2 records), GAN (Affinity Capture-MS; 2 records)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
Dynein-2 complex, cytoplasmic	12	DYNC2H1, DYNC2I1, DYNC2I2, DYNLL1, DYNLL2, DYNLRB1, DYNLT3, NUDCD3, DYNC2LI1, DYNLRB2, DYNLT1, DYNLT2B

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 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.

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	17	10.0×	7e-10
protein ubiquitination	16	7.4×	1e-07
ubiquitin-dependent protein catabolic process	8	6.7×	6e-03

Disease & clinical

Genetic variants

Variant evidence for NUDCD3: 56 ClinVar records (1 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	45
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3391111	NM_015332.4(NUDCD3):c.938A>C (p.His313Pro)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore NUDCD3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 977):

Position(s)	Effect	Δscore	Sites
7:44392318	donor_gain	1.0000
7:44392486–44392487	acceptor_loss	1.0000	5
7:44404452	donor_gain	1.0000
7:44427569–44427570	donor_loss	1.0000	5
7:44427704–44427705	acceptor_loss	1.0000	6
7:44490407–44490408	donor_loss	1.0000	5
7:44385999	donor_gain	0.9900
7:44392275	donor_gain	0.9900
7:44392486	acceptor_loss	0.9900
7:44404438–44404439	donor_loss	0.9900	5

AlphaMissense

889 missense substitutions predicted likely pathogenic (of 2,386 scored), across 205 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D39	8	0.993	0.996
F342	8	0.992	0.999
F33	8	0.985	0.999
D311	8	0.983	0.996
D10	8	0.981	0.995
F53	8	0.969	0.997
F26	8	0.961	0.995
F347	8	0.957	0.998
F352	8	0.954	0.997
F31	8	0.953	0.986
F40	8	0.948	0.997
N183	8	0.932	0.993
H323	8	0.895	0.977
H19	8	0.803	0.973
D198	8	0.794	0.936
D76	8	0.747	0.867
W335	7	0.995	0.999
W192	7	0.994	0.999
W273	7	0.992	0.999
W272	7	0.991	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000149
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000266
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.000315

Disease associations

OMIM: gene MIM:610296 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
severe combined immunodeficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
severe combined immunodeficiency	Limited	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (1): severe combined immunodeficiency (MONDO:0015974)

HPO phenotypes

28 phenotypes (HPO-id order):

HPO	Term
HP:0000100	Nephrotic syndrome
HP:0000821	Hypothyroidism
HP:0000944	Abnormal metaphysis morphology
HP:0000958	Dry skin
HP:0000969	Edema
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001072	Thickened skin
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001831	Short toe
HP:0001880	Increased total eosinophil count
HP:0001903	Anemia
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002028	Chronic diarrhea
HP:0002090	Pneumonia
HP:0002240	Hepatomegaly
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002960	Autoimmunity
HP:0004332	Abnormal lymphocyte morphology
HP:0004430	Severe combined immunodeficiency
HP:0007549	Desquamation of skin soon after birth
HP:0100646	Thyroiditis
HP:0100806	Sepsis
HP:0100840	Aplasia/Hypoplasia of the eyebrow

GWAS associations

2 associations:

Study	Trait	p-value
GCST006998_3	Cerebrospinal fluid p-tau levels in mild cognitive impairment	4e-7
GCST007741_32	Iris color (b* coordinate)	7e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004760	t-tau measurement
EFO:0009764	eye colour measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, decreases expression	3
Rotenone	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	decreases expression	1
picoxystrobin	decreases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Cadmium	increases abundance, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Methotrexate	decreases expression	1
Thiram	decreases expression	1
Fatty Acids, Omega-3	decreases expression	1
Copper Sulfate	decreases expression	1
Fatty Acids, Omega-6	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

44 trials:

NCT	Phase	Status	Title
NCT00220766	Phase 3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	Phase 3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	Phase 3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00000603	Phase 2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	Phase 2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	Phase 2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	Phase 2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	Phase 2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	Phase 2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	Phase 2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00008450	Phase 1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	Phase 1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	Phase 1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	Phase 1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT01019876	Phase 2/3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	Phase 1/2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	Phase 1/2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	Phase 1/2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	Phase 1/2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	Phase 1/2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	Phase 1/2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	Phase 1/2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	Phase 1/2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	Phase 1/2	ACTIVE_NOT_RECRUITING	Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT00001255	Not specified	COMPLETED	Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006335	Not specified	COMPLETED	Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID
NCT00055172	Not specified	RECRUITING	Genetic Basis of Immunodeficiency
NCT00695279	Not specified	COMPLETED	Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products
NCT00845416	Not specified	COMPLETED	Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02231983	Not specified	UNKNOWN	Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China
NCT02590328	Not specified	COMPLETED	Neonatal Screening of Severe Combined Immunodeficiencies
NCT04049084	Not specified	ENROLLING_BY_INVITATION	An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
NCT04172181	Not specified	UNKNOWN	Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID
NCT04246840	Not specified	COMPLETED	Study Through Imaging of Visceral Lymphoid Organs in Patients With SCID Who Have Recieved Bone Marrow Allograft
NCT04331483	Not specified	WITHDRAWN	A Study to Assess a Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Allografts
NCT05298930	Not specified	COMPLETED	Feasibility Study to Assess an Adapted Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Transplantation
NCT05651113	Not specified	RECRUITING	The Experience of Screening for SCID
NCT06659588	Not specified	RECRUITING	Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency
NCT06731036	Not specified	AVAILABLE	Expanded Access to CD34+ Selection Utilizing Miltenyi CliniMACS Prodigy® for Patients Receiving Peripheral Blood Stem Cell Transplantations and Stem Cell Boosts