CCDC8

Summary

CCDC8 (coiled-coil domain containing 8 subunit of 3M complex, HGNC:25367) is a protein-coding gene on chromosome 19q13.32, encoding Coiled-coil domain-containing protein 8 (Q9H0W5). Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity.

This gene encodes a coiled-coil domain-containing protein. The encoded protein functions as a cofactor required for p53-mediated apoptosis following DNA damage, and may also play a role in growth through interactions with the cytoskeletal adaptor protein obscurin-like 1. Mutations in this gene are a cause of 3M syndrome-3 (3M3).

Source: NCBI Gene 83987 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 3M syndrome 3 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 246 total — 1 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 51
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_032040

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25367
Approved symbol	CCDC8
Name	coiled-coil domain containing 8 subunit of 3M complex
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp564K0322, 3M3, PPP1R20, p90
Ensembl gene	ENSG00000169515
Ensembl biotype	protein_coding
OMIM	614145
Entrez	83987

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000307522, ENST00000697726

RefSeq mRNA: 1 — MANE Select: NM_032040 NM_032040

CCDS: CCDS12685

Canonical transcript exons

ENST00000307522 — 1 exons

Exon	Start	End
ENSE00001134624	46410329	46413564

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 97.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5021 / max 102.5117, expressed in 985 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181634	6.9059	956
181635	0.9310	523
181632	0.8723	504
181633	0.5891	433
181631	0.2039	119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	97.17	silver quality
upper arm skin	UBERON:0004263	94.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.81	gold quality
left ventricle myocardium	UBERON:0006566	94.57	gold quality
nasal cavity epithelium	UBERON:0005384	93.36	gold quality
vena cava	UBERON:0004087	92.78	silver quality
myocardium	UBERON:0002349	91.77	gold quality
heart right ventricle	UBERON:0002080	91.62	gold quality
saphenous vein	UBERON:0007318	91.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.58	gold quality
renal medulla	UBERON:0000362	90.07	gold quality
right uterine tube	UBERON:0001302	89.99	gold quality
body of tongue	UBERON:0011876	89.94	gold quality
cardia of stomach	UBERON:0001162	89.86	silver quality
epithelial cell of pancreas	CL:0000083	89.57	silver quality
tibia	UBERON:0000979	88.89	gold quality
trachea	UBERON:0003126	88.76	gold quality
subthalamic nucleus	UBERON:0001906	88.49	gold quality
cardiac atrium	UBERON:0002081	88.39	gold quality
ventral tegmental area	UBERON:0002691	88.20	silver quality
superior surface of tongue	UBERON:0007371	88.07	silver quality
pharyngeal mucosa	UBERON:0000355	88.00	gold quality
apex of heart	UBERON:0002098	87.94	gold quality
right atrium auricular region	UBERON:0006631	87.92	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.80	gold quality
fallopian tube	UBERON:0003889	87.72	gold quality
pericardium	UBERON:0002407	87.70	gold quality
right ovary	UBERON:0002118	87.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.63	gold quality
mammary duct	UBERON:0001765	87.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting CCDC8, 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-4282	99.99	75.36	6408
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-595	98.25	67.44	699
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-3650	97.88	64.89	693

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 10)

• We propose that CUL7, OBSL1, and CCDC8 are members of a pathway controlling mammalian growth. (PMID:21737058)
• p90 is a critical cofactor for p53-mediated apoptosis through promoting Tip60-mediated p53 acetylation. (PMID:22084066)
• discussion of roles of CCDC8, CUL7 (cullin 7), and OBSL1 (obscurin-like 1) in growth and development using findings from patients with Miller-McKusick-Malvaux syndrome and Silver-Russell syndrome [REVIEW] (PMID:22156540)
• Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signalling. (PMID:23018678)
• CUL7, OBSL1 and CCDC8 modulate the alternative splicing of the INSR (PMID:24711643)
• The CUL7, OBSL1, and CCDC8 proteins form a 3M complex that functions in maintaining microtubule and genome integrity and normal development. (PMID:24793695)
• CCDC8 may suppress the invasion and metastasis of non-small cell lung cancer cells. (PMID:27342910)
• Variants near TTN and CCDC8 were associated with KI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in hepatitis B-related hepatocellular carcinoma patients. (PMID:28700999)
• Overexpressed coiled-coil domain containing protein 8 (CCDC8) mediates newly synthesized HIV-1 Gag lysosomal degradation. (PMID:32651437)
• A rare cause of syndromic short stature: 3M syndrome in three families. (PMID:33258289)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccdc8	ENSMUSG00000041117
rattus_norvegicus	Ccdc8	ENSRNOG00000027936

Paralogs (13): MOAP1 (ENSG00000165943), ZCCHC18 (ENSG00000166707), ZCCHC12 (ENSG00000174460), PNMA1 (ENSG00000176903), PNMA8A (ENSG00000182013), PNMA3 (ENSG00000183837), PNMA5 (ENSG00000198883), PNMA8B (ENSG00000204851), PNMA6E (ENSG00000214897), PNMA6F (ENSG00000225110), PNMA6A (ENSG00000235961), PNMA2 (ENSG00000240694), PNMA8C (ENSG00000277531)

Protein

Protein identifiers

Coiled-coil domain-containing protein 8 — Q9H0W5 (reviewed: Q9H0W5)

All UniProt accessions (2): Q9H0W5, A0A8V8TMN3

UniProt curated annotations — full annotation on UniProt →

Function. Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer. Required for localization of CUL7 to the centrosome.

Subunit / interactions. Component of the 3M complex, composed of core components CUL7, CCDC8 and OBSL1. Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats); may link the 3M complex to histone deacetylases including HDAC4 and HDAC5.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Widely expressed with low levels in spleen, skeletal muscle, small intestine, kidney and liver.

Disease relevance. 3M syndrome 3 (3M3) [MIM:614205] A disorder characterized by poor postnatal growth and distinctive facial features, including triangular facies, frontal bossing, fleshy tipped nose, and fleshy lips. Other features may include skeletal anomalies and prominent heels. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2.

RefSeq proteins (1): NP_114429* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026526	CCDC8	Family

UniProt features (23 total): compositionally biased region 8, modified residue 3, sequence variant 3, region of interest 2, mutagenesis site 2, coiled-coil region 2, chain 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4LG6	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0W5-F1	46.83	0.00

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): 142, 146, 261

Mutagenesis-validated functional residues (2):

Position	Phenotype
503	decreased interaction with ankra2.
504	decreased interaction with ankra2.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 180 (showing top): GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOCC_MICROTUBULE_ORGANIZING_CENTER, NFKB_C, GOBP_ORGANELLE_FISSION, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_MITOTIC_CELL_CYCLE, PIT1_Q6, CCCNNGGGAR_OLF1_01, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_MITOTIC_CELL_CYCLE, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (2): microtubule cytoskeleton organization (GO:0000226), regulation of mitotic nuclear division (GO:0007088)

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

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), 3M complex (GO:1990393), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoskeleton organization	1
microtubule-based process	1
regulation of mitotic cell cycle	1
regulation of cell cycle process	1
regulation of nuclear division	1
mitotic nuclear division	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
membrane	1
cell periphery	1
protein-containing complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC8	OBSL1	O75147	977
CCDC8	CUL7	Q14999	922
CCDC8	ANKRA2	Q9H9E1	627
CCDC8	GALNT9	Q9HCQ5	571
CCDC8	KAT5	Q92993	503
CCDC8	CUL9	Q8IWT3	483
CCDC8	KLHL35	Q6PF15	483
CCDC8	FBXW8	Q8N3Y1	474
CCDC8	CCDC34	Q96HJ3	471
CCDC8	CCDC106	Q9BWC9	463
CCDC8	SDR42E1	Q8WUS8	461
CCDC8	PKN3	Q6P5Z2	457
CCDC8	EFEMP1	Q12805	457
CCDC8	TPM2	P06468	452
CCDC8	CCDC178	Q5BJE1	447

IntAct

80 interactions, top by confidence:

A	B	Type	Score
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
ANKRA2	CCDC8	psi-mi:“MI:0915”(physical association)	0.640
CCDC8	ANKRA2	psi-mi:“MI:0407”(direct interaction)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
IL20RA	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
NHLH2	AP3B1	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CASQ2	PES1	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
CCDC8	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
PB2	IPO5	psi-mi:“MI:0914”(association)	0.350
PB2	HAX1	psi-mi:“MI:0914”(association)	0.350
FBXW8	PDCD5	psi-mi:“MI:0914”(association)	0.350

BioGRID (739): SCRIB (Affinity Capture-MS), AARS2 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABCF2 (Affinity Capture-MS), ABLIM1 (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACLY (Affinity Capture-MS), ACSL3 (Affinity Capture-MS), ACTC1 (Affinity Capture-MS), ACTG1 (Affinity Capture-MS), ACTN4 (Affinity Capture-MS), ADNP (Affinity Capture-MS), AFG3L2 (Affinity Capture-MS), AGPS (Affinity Capture-MS), AHNAK (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQG5, A1L429, A6NDE8, A6NER3, A6NGK3, E1AZ71, O08664, O60829, O75459, O76087, P0C2W7, P0CL80, P0CL81, P0CL82, P0DSO3, P0DTW1, P52651, P62521, P86478, P86479, P86480, P86481, P86496, Q13066, Q13069, Q13070, Q17QW4, Q28181, Q2T9P9, Q32PA2, Q4V321, Q4V326, Q5JQC4, Q5U2Y8, Q62100, Q63803, Q64256, Q6NT46, Q6X7S9, Q7Z2X7

Diamond homologs: A0A0J9YX94, A0A0J9YXQ4, A0A1B0GUJ8, A6QLK5, A7E321, D3YZV8, P0CW24, P62521, Q2KIT6, Q5DTT8, Q5R486, Q5R6R8, Q80VM8, Q86V59, Q8BHK0, Q8C1C8, Q8JZW8, Q8ND90, Q8VHZ4, Q95KI4, Q96BY2, Q96PV4, Q9ERH6, Q9GMU3, Q9H0W5, Q9UL41, Q9UL42, Q9ULN7, P0CG32, Q08DL1, Q5HZA3, Q6PEW1, Q8VD24, Q9CZA5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	14.0×	4e-04
SARS-CoV-1-host interactions	6	13.7×	5e-04
G2/M Checkpoints	6	10.5×	2e-03
Programmed Cell Death	5	9.5×	7e-03
SARS-CoV-1 Infection	5	9.3×	8e-03
Cell Cycle Checkpoints	6	6.9×	8e-03
RHO GTPase Effectors	7	6.2×	6e-03
Membrane Trafficking	9	4.3×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
substantia nigra development	5	19.1×	1e-03
long-term synaptic potentiation	5	14.6×	2e-03
intracellular protein localization	7	7.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	8
Uncertain significance	159
Likely benign	48
Benign	16

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
31105	NM_032040.5(CCDC8):c.84dup (p.Lys29Ter)	Pathogenic
1028424	NM_032040.5(CCDC8):c.803_807delinsT (p.Lys268fs)	Likely pathogenic
3065843	NM_032040.5(CCDC8):c.324_331del (p.Ser108fs)	Likely pathogenic
31104	NM_032040.5(CCDC8):c.612dup (p.Lys205fs)	Likely pathogenic
3374708	NM_032040.5(CCDC8):c.1057del (p.Ala353fs)	Likely pathogenic
4293702	NM_032040.5(CCDC8):c.83_86dup (p.Lys29delinsAsnTer)	Likely pathogenic
4535004	NM_032040.5(CCDC8):c.608G>A (p.Trp203Ter)	Likely pathogenic
931927	NM_032040.5(CCDC8):c.203_204del (p.Gln68fs)	Likely pathogenic
993034	NM_032040.5(CCDC8):c.963del (p.Ala323fs)	Likely pathogenic

SpliceAI

51 predictions. Top by Δscore:

Variant	Effect	Δscore
19:46410681:G:GC	acceptor_gain	0.9300
19:46410681:G:C	acceptor_gain	0.9000
19:46410688:C:CT	acceptor_gain	0.8200
19:46410679:G:GC	acceptor_gain	0.7800
19:46410679:G:C	acceptor_gain	0.7500
19:46410689:A:T	acceptor_gain	0.7200
19:46413518:G:T	donor_gain	0.6900
19:46412931:C:G	acceptor_gain	0.6400
19:46412225:C:CA	donor_gain	0.6100
19:46412930:T:TG	acceptor_gain	0.6100
19:46410684:C:CT	acceptor_gain	0.5700
19:46410675:T:TC	acceptor_gain	0.4800
19:46412229:C:CT	donor_gain	0.4800
19:46412928:GCTCC:G	acceptor_gain	0.4800
19:46413353:T:TA	donor_gain	0.4600
19:46412230:C:CT	donor_gain	0.4500
19:46412932:C:CT	acceptor_gain	0.4500
19:46410685:A:T	acceptor_gain	0.4400
19:46410597:G:C	acceptor_gain	0.4300
19:46410674:A:C	acceptor_gain	0.4200
19:46412909:CTT:C	acceptor_gain	0.4000
19:46412910:TTT:T	acceptor_gain	0.4000
19:46412926:ACGCT:A	acceptor_gain	0.3900
19:46412927:CGCTC:C	acceptor_gain	0.3900
19:46412911:T:G	acceptor_gain	0.3800
19:46412222:A:AC	donor_gain	0.3700
19:46412223:C:CC	donor_gain	0.3700
19:46413049:GCCCC:G	acceptor_gain	0.3700
19:46412929:CTCCA:C	acceptor_gain	0.3600
19:46412921:C:CT	acceptor_gain	0.3400

AlphaMissense

3500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:46412679:G:C	F44L	0.994
19:46412679:G:T	F44L	0.994
19:46412681:A:G	F44L	0.994
19:46412741:A:G	W24R	0.993
19:46412741:A:T	W24R	0.993
19:46412680:A:G	F44S	0.992
19:46412700:A:C	F37L	0.991
19:46412700:A:T	F37L	0.991
19:46412702:A:G	F37L	0.991
19:46412394:G:C	F139L	0.990
19:46412394:G:T	F139L	0.990
19:46412396:A:G	F139L	0.990
19:46412739:C:A	W24C	0.986
19:46412739:C:G	W24C	0.986
19:46411371:G:C	F480L	0.984
19:46411371:G:T	F480L	0.984
19:46411373:A:G	F480L	0.984
19:46412680:A:C	F44C	0.983
19:46412412:G:C	S133R	0.982
19:46412412:G:T	S133R	0.982
19:46412414:T:G	S133R	0.982
19:46412724:C:A	K29N	0.982
19:46412724:C:G	K29N	0.982
19:46412689:A:G	L41P	0.981
19:46412343:G:C	F156L	0.980
19:46412343:G:T	F156L	0.980
19:46412345:A:G	F156L	0.980
19:46412773:A:G	I13T	0.979
19:46412734:A:T	V26D	0.978
19:46412662:C:G	R50P	0.977

dbSNP variants (sampled 300 via entrez): RS1000195655 (19:46413757 C>A), RS1000957663 (19:46415261 A>G), RS1001146183 (19:46415381 T>C), RS1001307332 (19:46410017 C>T), RS1001818994 (19:46412988 G>A), RS1002198323 (19:46414855 G>A), RS1003248316 (19:46413476 G>A,C), RS1003607047 (19:46413636 T>C), RS1004186543 (19:46414306 G>A,T), RS1004301334 (19:46414576 T>C), RS1005033414 (19:46410527 A>G), RS1005560965 (19:46410646 T>C), RS1005820988 (19:46414128 G>A,C), RS1007496329 (19:46414217 G>A), RS1008161841 (19:46411828 C>G,T)

Disease associations

OMIM: gene MIM:614145 | disease phenotypes: MIM:614205, MIM:300755

GenCC curated gene-disease

Disease	Classification	Inheritance
3M syndrome 3	Strong	Autosomal recessive
3-M syndrome	Supportive	Autosomal recessive
spinocerebellar ataxia type 40	Limited	Autosomal dominant

Mondo (4): 3M syndrome 3 (MONDO:0013627), immunodeficiency disease (MONDO:0021094), spinocerebellar ataxia type 40 (MONDO:0014475), 3-M syndrome (MONDO:0007477)

Orphanet (1): 3M syndrome (Orphanet:2616)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000144	Decreased fertility
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000307	Pointed chin
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000574	Thick eyebrow
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000883	Thin ribs
HP:0000888	Horizontal ribs
HP:0000944	Abnormal metaphysis morphology
HP:0001374	Congenital hip dislocation
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001838	Rocker bottom foot
HP:0002007	Frontal bossing
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003542_198	Night sleep phenotypes	3.000000e-06
GCST004132_48	Crohn’s disease	4.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535314	Miller-McKusick-Malvaux-Syndrome (3M Syndrome) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	increases expression	1
ferrous chloride	decreases expression	1
hydroquinone	decreases expression	1
clothianidin	increases expression	1
Cannabidiol	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Silicon Dioxide	decreases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Dronabinol	decreases expression	1
Valproic Acid	increases expression	1
Vanadates	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Antirheumatic Agents	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001542	PHASE4	COMPLETED	Fluconazole Prophylaxis of Thrush in AIDS
NCT00144157	PHASE4	COMPLETED	Open Label Study of NVP+CBV Treatment in Women Who Have Received sdNVP for the pMTCT of HIV
NCT00162643	PHASE4	UNKNOWN	PI Vs. NNRTI Based Therapy for HIV Advanced Disease
NCT00273988	PHASE4	COMPLETED	Pharmacokinetic Study of Interaction Between Nevirapine and Methadone in HIV-1 Infected, Opioid-dependent Adults
NCT00981318	PHASE4	TERMINATED	Pilot Assessment of Lopinavir/Ritonavir and Maraviroc
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01090102	PHASE4	COMPLETED	Mesalamine to Reduce T Cell Activation in HIV Infection
NCT01147042	PHASE4	TERMINATED	Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease
NCT01230580	PHASE4	UNKNOWN	Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
NCT01465958	PHASE4	COMPLETED	Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
NCT02274662	PHASE4	COMPLETED	Expanded Access Protocol Thymus Transplantation
NCT02348177	PHASE4	COMPLETED	Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
NCT02396979	PHASE4	COMPLETED	Intervention of HIV, Drug Use and the Criminal Justice System in Malaysia
NCT02490956	PHASE4	UNKNOWN	Diagnostic Immunization With Rabies Vaccine in Patients With PID
NCT02503293	PHASE4	COMPLETED	A Study to Compare Quality of Life and Satisfaction in Primary Immunodeficient Patients Treated With Subcutaneous Injections of Gammanorm® 165 mg/mL Administered With Two Different Delivery Devices: Injections Using Pump or Rapid Push
NCT02881437	PHASE4	COMPLETED	IgG Level in Primary Immunodeficiency Switching From Standard SCIG to Every Other Week HyQvia
NCT03033745	PHASE4	COMPLETED	Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT04192487	PHASE4	COMPLETED	Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
NCT04566692	PHASE4	COMPLETED	A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
NCT05493969	PHASE4	NOT_YET_RECRUITING	Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
NCT06576024	PHASE4	COMPLETED	Immunogenicity and Safety of Inactivated Hepatitis A Vaccine in HIV-infected People
NCT06634641	PHASE4	RECRUITING	Clozapine-related Immunodeficiency in Parkinsons Disease
NCT07076446	PHASE4	ACTIVE_NOT_RECRUITING	An Open-label, Multicenter Study to Assess the Pharmacokinetics (PK), Safety, and Tolerability of Subcutaneous IgPro20 in Immunoglobulin (IG) Treatment-naïve Participants With Primary Immunodeficiency (PID)
NCT00000118	PHASE3	COMPLETED	Ganciclovir Implant Study for Cytomegalovirus Retinitis
NCT00000134	PHASE3	COMPLETED	Studies of the Ocular Complications of AIDS (SOCA)–Cytomegalovirus Retinitis Retreatment Trial (CRRT)
NCT00000590	PHASE3	COMPLETED	Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
NCT00001267	PHASE3	COMPLETED	A Randomized Pilot Study for the Treatment of AIDS or AIDS Related Complex With an Alternating or Simultaneous Combination Regimen of AZT and 2’,3’-Dideoxyinosine
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00144183	PHASE3	COMPLETED	A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)
NCT00243568	PHASE3	WITHDRAWN	Vicriviroc, a CCR5 Inhibitor, Added to an Optimized Antiretroviral Therapy for Previously Treated HIV (VICTOR-E2) (Study P04285
NCT00278954	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT00474370	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04889AM8)(COMPLETED)
NCT00478231	PHASE3	COMPLETED	Multicenter, Safety Study Of Maraviroc
NCT00523211	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04405AM5)
NCT00698334	PHASE3	COMPLETED	Efficacy of Thrice Weekly Directly Observed Treatment, Short-course (DOTS) in HIV-associated Tuberculosis
NCT00966160	PHASE3	COMPLETED	CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes
NCT01363011	PHASE3	COMPLETED	Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
NCT01440569	PHASE3	COMPLETED	Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
NCT01475838	PHASE3	COMPLETED	Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients