CCDC47

Summary

CCDC47 (coiled-coil domain containing 47, HGNC:24856) is a protein-coding gene on chromosome 17q23.3, encoding PAT complex subunit CCDC47 (Q96A33). Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes.

Enables protein folding chaperone and ribosome binding activity. Involved in ERAD pathway; endoplasmic reticulum calcium ion homeostasis; and multi-pass transmembrane protein insertion into ER membrane. Located in endoplasmic reticulum membrane. Part of multi-pass translocon complex.

Source: NCBI Gene 57003 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): trichohepatoneurodevelopmental syndrome (Definitive, GenCC)
• Clinical variants (ClinVar): 89 total — 1 pathogenic, 5 likely-pathogenic
• GTEx eGene: eQTL in 22 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 82
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.92 (unconstrained)
• MANE Select transcript: NM_020198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24856
Approved symbol	CCDC47
Name	coiled-coil domain containing 47
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	GK001
Ensembl gene	ENSG00000108588
Ensembl biotype	protein_coding
OMIM	618260
Entrez	57003

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 33 protein_coding, 7 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000225726

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

ENST00000225726, ENST00000403162, ENST00000580986, ENST00000582252, ENST00000582331, ENST00000584112, ENST00000878791, ENST00000878792, ENST00000878793, ENST00000878794, ENST00000878795, ENST00000878796, ENST00000878797, ENST00000878798, ENST00000878799, ENST00000878800, ENST00000878801, ENST00000916946, ENST00000916947, ENST00000916948, ENST00000916949, ENST00000960669, ENST00000960670, ENST00000960671, ENST00000960672, ENST00000960673, ENST00000960674, ENST00000960675, ENST00000960676, ENST00000960677, ENST00000960678, ENST00000998864, ENST00000998867, ENST00001025917, ENST00001025919, ENST00001025920, ENST00001025921, ENST00001086069, ENST00001086070, ENST00001099459, ENST00001113617, ENST00001137760

RefSeq mRNA: 1 — MANE Select: NM_020198 NM_020198

CCDS: CCDS11643

Canonical transcript exons

ENST00000225726 — 13 exons

Exon	Start	End
ENSE00000555654	63761230	63761351
ENSE00000742037	63751940	63752107
ENSE00000742039	63752741	63752799
ENSE00000742049	63764016	63764190
ENSE00000742051	63764740	63764847
ENSE00000742053	63765912	63766194
ENSE00000857864	63752320	63752429
ENSE00000857866	63754433	63754518
ENSE00001347617	63745255	63746961
ENSE00001553059	63773412	63773597
ENSE00003468323	63756469	63756570
ENSE00003560640	63760914	63760979
ENSE00003664439	63756240	63756350

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.2546 / max 1010.8774, expressed in 1826 samples.

Highest expression (Bgee): calcaneal tendon, islet of Langerhans, rectum, tendon, heart right ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CCDC47 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	7.1e-10	-0.37	17:63863361:G:A
Esophagus Mucosa	eqtl	1.1e-08	+0.09	17:63889464:C:T
Testis	eqtl	2.4e-08	-0.11	17:63710324:T:C
Cells Cultured fibroblasts	eqtl	4.8e-06	+0.08	17:63846478:G:A
Heart Atrial Appendage	eqtl	1.0e-05	+0.09	17:63863361:G:A
Pancreas	eqtl	2.2e-05	+0.14	17:63890753:G:C
Stomach	eqtl	2.7e-05	+0.12	17:63638101:G:A
Cells EBV-transformed lymphocytes	sqtl	4.9e-05	+0.45	17:63814024:G:A
Artery Aorta	eqtl	5.3e-04	+0.08	17:63889464:C:T
Skin Not Sun Exposed Suprapubic	eqtl	5.7e-04	+0.08	17:63571559:G:A
Skin Sun Exposed Lower leg	eqtl	1.5e-03	+0.06	17:63706193:T:G
Whole Blood	eqtl	1.9e-03	+0.14	17:63663753:G:A
Brain Cortex	eqtl	4.3e-03	+0.73	17:63863394:C:T
Skin Not Sun Exposed Suprapubic	sqtl	4.8e-03	-1.08	17:64274667:G:A
Minor Salivary Gland	eqtl	5.5e-03	-0.95	17:63444584:G:A
Brain Amygdala	eqtl	8.0e-03	-0.44	17:64377617:A:AAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGG
Artery Tibial	eqtl	9.5e-03	+0.14	17:63558169:C:T
Lung	eqtl	1.0e-02	-0.06	17:63901405:G:A
Colon Transverse	eqtl	1.7e-02	+0.07	17:63621363:A:G
Nerve Tibial	eqtl	1.8e-02	+0.06	17:63919139:C:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
167484	80.9105	1826
167485	0.3441	172

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.03	gold quality
islet of Langerhans	UBERON:0000006	97.79	gold quality
rectum	UBERON:0001052	97.30	gold quality
tendon	UBERON:0000043	97.29	gold quality
heart right ventricle	UBERON:0002080	97.19	gold quality
parotid gland	UBERON:0001831	96.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.99	gold quality
colonic mucosa	UBERON:0000317	96.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.57	gold quality
biceps brachii	UBERON:0001507	96.48	gold quality
gastrocnemius	UBERON:0001388	96.47	gold quality
muscle of leg	UBERON:0001383	96.33	gold quality
cervix squamous epithelium	UBERON:0006922	96.10	gold quality
cartilage tissue	UBERON:0002418	96.04	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.99	gold quality
palpebral conjunctiva	UBERON:0001812	95.89	gold quality
tendon of biceps brachii	UBERON:0008188	95.89	gold quality
colonic epithelium	UBERON:0000397	95.79	gold quality
left adrenal gland	UBERON:0001234	95.60	gold quality
pancreas	UBERON:0001264	95.54	gold quality
adrenal gland	UBERON:0002369	95.43	gold quality
gall bladder	UBERON:0002110	95.41	gold quality
right adrenal gland	UBERON:0001233	95.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.40	gold quality
adrenal tissue	UBERON:0018303	95.33	gold quality
left adrenal gland cortex	UBERON:0035825	95.28	gold quality
right adrenal gland cortex	UBERON:0035827	95.24	gold quality
right atrium auricular region	UBERON:0006631	95.13	gold quality
duodenum	UBERON:0002114	95.12	gold quality
stromal cell of endometrium	CL:0002255	95.11	gold quality
choroid plexus epithelium	UBERON:0003911	95.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.02	gold quality
germinal epithelium of ovary	UBERON:0001304	94.96	gold quality
adrenal cortex	UBERON:0001235	94.92	gold quality
jejunal mucosa	UBERON:0000399	94.90	gold quality
cardiac ventricle	UBERON:0002082	94.90	gold quality
heart left ventricle	UBERON:0002084	94.90	gold quality
ventricular zone	UBERON:0003053	94.89	gold quality
cardiac atrium	UBERON:0002081	94.83	gold quality
body of pancreas	UBERON:0001150	94.82	gold quality
eye	UBERON:0000970	94.63	gold quality
heart	UBERON:0000948	94.54	gold quality
oviduct epithelium	UBERON:0004804	94.33	gold quality
jejunum	UBERON:0002115	94.31	gold quality
medial globus pallidus	UBERON:0002477	94.25	gold quality
corpus callosum	UBERON:0002336	94.22	gold quality
transverse colon	UBERON:0001157	94.18	gold quality
saliva-secreting gland	UBERON:0001044	94.17	gold quality
upper arm skin	UBERON:0004263	94.07	gold quality
mucosa of transverse colon	UBERON:0004991	93.85	gold quality
minor salivary gland	UBERON:0001830	93.81	gold quality
caudate nucleus	UBERON:0001873	93.81	gold quality
lower lobe of lung	UBERON:0008949	93.74	gold quality
upper lobe of left lung	UBERON:0008952	93.74	gold quality
upper lobe of lung	UBERON:0008948	93.70	gold quality
placenta	UBERON:0001987	93.67	gold quality
large intestine	UBERON:0000059	93.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.62	gold quality
nasal cavity mucosa	UBERON:0001826	93.57	gold quality
colon	UBERON:0001155	93.55	gold quality
fallopian tube	UBERON:0003889	93.54	gold quality
liver	UBERON:0002107	93.49	gold quality
vena cava	UBERON:0004087	93.49	gold quality
ileal mucosa	UBERON:0000331	93.45	gold quality
globus pallidus	UBERON:0001875	93.45	gold quality
mouth mucosa	UBERON:0003729	93.45	gold quality
intestine	UBERON:0000160	93.44	gold quality
prefrontal cortex	UBERON:0000451	93.41	gold quality
endometrium	UBERON:0001295	93.39	gold quality
squamous epithelium	UBERON:0006914	93.38	gold quality
tonsil	UBERON:0002372	93.35	gold quality
body of stomach	UBERON:0001161	93.34	gold quality
lung	UBERON:0002048	93.32	gold quality
urinary bladder	UBERON:0001255	93.29	gold quality
gingival epithelium	UBERON:0001949	93.26	gold quality
putamen	UBERON:0001874	93.18	gold quality
spinal cord	UBERON:0002240	93.16	gold quality
stomach	UBERON:0000945	93.15	gold quality
monocyte	CL:0000576	93.13	gold quality
skin of hip	UBERON:0001554	93.13	gold quality
myocardium	UBERON:0002349	93.13	gold quality
thoracic mammary gland	UBERON:0005200	93.11	gold quality
descending thoracic aorta	UBERON:0002345	93.09	gold quality
right lung	UBERON:0002167	93.06	gold quality
gingiva	UBERON:0001828	93.04	gold quality
cerebellar vermis	UBERON:0004720	93.03	gold quality
mammary gland	UBERON:0001911	93.01	gold quality
mononuclear cell	CL:0000842	93.00	gold quality
peritoneum	UBERON:0002358	92.96	gold quality
omental fat pad	UBERON:0010414	92.96	gold quality
body of tongue	UBERON:0011876	92.95	gold quality
nucleus accumbens	UBERON:0001882	92.91	gold quality
vermiform appendix	UBERON:0001154	92.90	gold quality
skeletal muscle organ	UBERON:0014892	92.86	gold quality
muscle organ	UBERON:0001630	92.84	gold quality
esophagus mucosa	UBERON:0002469	92.83	gold quality
small intestine	UBERON:0002108	92.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.76	gold quality
leukocyte	CL:0000738	92.75	gold quality
sural nerve	UBERON:0015488	92.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	no	3.17
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	98.6
Skeletal muscle	tissue	93.0	medium
Liver	tissue	92.5	medium
Caudate putamen	tissue	90.3
Hippocampal formation	tissue	80.2
Parathyroid gland	tissue	79.5	medium
Duodenum	tissue	79.4	high
Tongue	tissue	78.1
Colon	tissue	75.8	high
Rectum	tissue	75.6	high
Frontal cortex	tissue	73.4
Stomach 1	tissue	72.0	high
Small intestine	tissue	70.6	high
Nucleus accumbens	tissue	66.0
Kidney	tissue	65.5	medium
Postcentral gyrus	tissue	63.1
Heart muscle	tissue	60.2	medium
Cerebral cortex	tissue	60.1	high
Somatosensory cortex	tissue	60.1
Adrenal gland	tissue	59.7	medium
Thyroid gland	tissue	57.9	medium
Hippocampus	tissue	57.5	high
Salivary gland	tissue	56.7	high
Superior colliculi	tissue	56.1
Occipital cortex	tissue	56.1
Pons	tissue	55.1
Prostate	tissue	55.1	medium
Pancreas	tissue	54.5	high
Urinary bladder	tissue	54.1	medium
Thalamus	tissue	54.1
Breast	tissue	53.4	high
Adipose tissue	tissue	52.9	not detected
Motor cortex	tissue	52.9
Putamen	tissue	52.9
Midbrain	tissue	51.2
Medulla oblongata	tissue	51.0
Placenta	tissue	50.6	high
Locus coeruleus	tissue	50.4
Septum	tissue	50.0
Spinal cord	tissue	49.9
Periaqueductal gray	tissue	49.8
Seminal vesicle	tissue	49.0	high
Lung	tissue	48.9	high
Skin 1	tissue	48.7	medium
Prefrontal cortex	tissue	48.1
Entorhinal cortex	tissue	47.7
Esophagus	tissue	47.6	high
Hypothalamus	tissue	47.6
Retrosplenial and cingulate cortex	tissue	47.6
Epididymis	tissue	47.4	high
Substantia nigra	tissue	47.1
Temporal cortex	tissue	45.8
Retrosplenial cortex	tissue	45.3
Cerebellum	tissue	45.1	high
Ventral forebrain	tissue	44.9
Cervix	tissue	44.8	medium
Gallbladder	tissue	44.0	high
Basal ganglia	tissue	43.8	medium
Amygdala	tissue	42.3
Retina	tissue	42.0

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal hippocampus (80.2), Corpus callosum, genu (white matter) (69.9), Caudate nucleus (69.6), Corpus callosum, splenium (white matter) (68.7), Ventral hippocampus (67.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CCDC47 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 147 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Functional genomics

gnomAD constraint: pLI 5.43e-09, LOEUF 0.918, missense Z 1.2 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000225726 — one region, missense o/e 0.88.

Literature-anchored findings (GeneRIF, showing 1)

• these findings suggested that calumin serves to maintain the yolk sac integrity through participation in the ERAD activity, contributing to embryonic development. (PMID:25009997)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc47	ENSDARG00000054362
mus_musculus	Ccdc47	ENSMUSG00000078622
rattus_norvegicus	Ccdc47	ENSRNOG00000009006
drosophila_melanogaster	CG17593	FBGN0031544
caenorhabditis_elegans		WBGENE00014204

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914413) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal cell physiology	1
neonatal lethality, complete penetrance	1
prenatal lethality, incomplete penetrance	1
increased fibroblast apoptosis	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
Macaca fascicularis	P0C204	99.6%	Diamond
Canis lupus familiaris	A0A8I3P7X4	98.8%	Diamond
Bos taurus	Q3ZC50	97.9%	Diamond
Pongo abelii	Q5RCI4	95.9%	Diamond
Xenopus laevis	Q6AZI2	77.9%	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
FTSJ3	protein-coding	117246
PSMC5	protein-coding	5705
SMARCD2	protein-coding	6603
STRADA	protein-coding	92335
DDX42	protein-coding	11325
MAP3K3	protein-coding	4215
LIMD2	protein-coding	80774

Protein

Protein identifiers

PAT complex subunit CCDC47 — Q96A33 (reviewed: Q96A33)

Alternative names: Calumin, Coiled-coil domain-containing protein 47

All UniProt accessions (2): Q96A33, J3KRX4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions. Within the MPT complex, the PAT subcomplex sequesters any highly polar regions in the transmembrane domains away from the non-polar membrane environment until they can be buried in the interior of the fully assembled protein. Within the PAT subcomplex, CCDC47 occludes the lateral gate of the SEC61 complex. Involved in the regulation of calcium ion homeostasis in the ER. Required for proper protein degradation via the ERAD (ER-associated degradation) pathway. Has an essential role in the maintenance of ER organization during embryogenesis.

Subunit / interactions. Component of the PAT complex, composed of WDR83OS/Asterix and CCDC47. The PAT complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex. Interacts with VCP, HSPA5, DERL1, DERL2 and SELENOS.

Subcellular location. Endoplasmic reticulum membrane. Rough endoplasmic reticulum membrane.

Disease relevance. Trichohepatoneurodevelopmental syndrome (THNS) [MIM:618268] An autosomal recessive complex multisystem disorder characterized by woolly or coarse hair, liver dysfunction, pruritus, dysmorphic features, hypotonia, and global developmental delay. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CCDC47 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96A33-1	1	yes
Q96A33-2	2

RefSeq proteins (1): NP_064583* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012879	CCDC47	Family

Pfam: PF07946

UniProt features (17 total): compositionally biased region 4, sequence variant 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, sequence conflict 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
6W6L	Cryo-EM structure of the human ribosome-TMCO1 translocon	ELECTRON MICROSCOPY	3.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96A33-F1	77.07	0.46

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): endoplasmic reticulum

Antibody reliability (HPA): IH approved · IF enhanced

Functional residue map

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

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	178

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: 424 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, ACTACCT_MIR196A_MIR196B, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_PROTEIN_MATURATION, GOBP_ER_NUCLEUS_SIGNALING_PATHWAY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_PROTEIN_FOLDING, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_CALCIUM_ION_HOMEOSTASIS, GOBP_OSSIFICATION, TCCAGAT_MIR5165P, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (6): osteoblast differentiation (GO:0001649), endoplasmic reticulum calcium ion homeostasis (GO:0032469), ERAD pathway (GO:0036503), protein insertion into ER membrane (GO:0045048), multi-pass transmembrane protein insertion into ER membrane (GO:0160063), protein folding (GO:0006457)

GO Molecular Function (5): RNA binding (GO:0003723), calcium ion binding (GO:0005509), ribosome binding (GO:0043022), protein folding chaperone (GO:0044183), protein binding (GO:0005515)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), rough endoplasmic reticulum membrane (GO:0030867), multi-pass translocon complex (GO:0160064), rough endoplasmic reticulum (GO:0005791)

GO top-level categories

30 GO namespaces:

Category	Terms
endoplasmic reticulum	2
ossification	1
cell differentiation	1
intracellular calcium ion homeostasis	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
endoplasmic reticulum organization	1
protein localization to organelle	1
protein insertion into membrane	1
protein insertion into ER membrane	1
cellular process	1
protein maturation	1
nucleic acid binding	1
metal ion binding	1
ribonucleoprotein complex binding	1
molecular_function	1
protein folding	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
endoplasmic reticulum membrane	1
rough endoplasmic reticulum	1
bounding membrane of organelle	1
ER membrane insertion complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
ERAD pathway	BP	mutant phenotype
endoplasmic reticulum calcium ion homeostasis	BP	mutant phenotype
multi-pass transmembrane protein insertion into ER membrane	BP	direct assay
osteoblast differentiation	BP	high-throughput assay
protein insertion into ER membrane	BP	direct assay
endoplasmic reticulum	CC	direct assay
endoplasmic reticulum membrane	CC	direct assay
membrane	CC	high-throughput assay
multi-pass translocon complex	CC	direct assay
RNA binding	MF	high-throughput assay
protein folding chaperone	MF	direct assay
ribosome binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,424 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC47	NCLN	Q969V3	715
CCDC47	TMEM147	Q9BVK8	702
CCDC47	TMCO1	Q9UM00	702
CCDC47	WDR83OS	Q9Y284	632
CCDC47	SEC61A1	P38378	618
CCDC47	EMC3	Q9P0I2	566
CCDC47	EMC6	Q9BV81	490
CCDC47	STT3A	P46977	479
CCDC47	EMC2	Q15006	473
CCDC47	CCDC172	P0C7W6	462
CCDC47	DNAJC10	Q8IXB1	462
CCDC47	BCAP29	Q9UHQ4	454
CCDC47	TRAM2	Q15035	452
CCDC47	BPNT2	Q9NX62	452
CCDC47	SEC61A2	Q9H9S3	448

IntAct

Human interaction partners of CCDC47 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

25 partners by confidence:

Partner	Interaction type	MIscore	Records
KAT5	physical association	0.560	3
LMO3	physical association	0.560	3
PRKCA	physical association	0.560	3
SETDB1	physical association	0.560	3
YWHAG	physical association	0.560	3
WDR83OS	physical association	0.560	2
IRF7	physical association	0.500	1
STING1	physical association	0.500	1
TIRAP	physical association	0.500	1
CEP162	physical association	0.400	1
IRAK2	physical association	0.400	1
MAP7D1	physical association	0.400	1
MFI	physical association	0.400	1
MPO	physical association	0.400	1
PTPRS	physical association	0.400	1
RPS6KB2	physical association	0.400	1
SCCPDH	physical association	0.400	1
ESYT2	association	0.350	1
ARF6	physical association	0.000	1
GSTK1	physical association	0.000	1
MAGEA6	physical association	0.000	1
PHLDA3	physical association	0.000	1
RPL7A	physical association	0.000	1
TMBIM4	physical association	0.000	1
TOM1L1	physical association	0.000	1

BioGRID (627 interactions; top human partners by supporting records in a sample of 600 records): ATP2C2 (Proximity Label-MS; 5 records), RPN1 (Co-fractionation; 4 records), SEC61B (Proximity Label-MS; 4 records), STIM1 (Proximity Label-MS; 4 records), TMCO1 (Affinity Capture-MS; 4 records), CANX (Proximity Label-MS; 3 records), EMC2 (Affinity Capture-MS; 3 records), MMGT1 (Affinity Capture-MS; 3 records), NCLN (Affinity Capture-Western; 3 records), PTPN1 (Affinity Capture-MS; 3 records), RPN2 (Proximity Label-MS; 3 records), VAPA (Proximity Label-MS; 3 records), CDC42 (Affinity Capture-MS; 2 records), CKAP4 (Proximity Label-MS; 2 records), DDOST (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CCDC47	“form complex”	“PAT intramembrane chaperone complex”	binding

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
PAT complex	2	CCDC47, WDR83OS

Disease & clinical

Genetic variants

Variant evidence for CCDC47: 89 ClinVar records (6 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	5
Uncertain significance	52
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (6)

Showing all 6 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
1697227	NM_020198.3(CCDC47):c.563del (p.Asn188fs)	Pathogenic	criteria provided, single submitter	1
562185	NM_020198.3(CCDC47):c.1165del (p.Ser389fs)	Likely pathogenic	criteria provided, single submitter	2
562186	NM_020198.3(CCDC47):c.811C>T (p.Arg271Ter)	Likely pathogenic	criteria provided, single submitter	2
562187	NM_020198.3(CCDC47):c.1145del (p.Leu382fs)	Likely pathogenic	criteria provided, single submitter	2
993035	NM_020198.3(CCDC47):c.567_570del (p.Glu190fs)	Likely pathogenic	criteria provided, single submitter	2
1526240	NM_020198.3(CCDC47):c.1211_1232dup (p.Ala411_Arg412insLysSerArgTer)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CCDC47’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; 27 predictions of 1,096):

Position(s)	Effect	Δscore	Sites
17:63751938–63751939	donor_loss	1.0000	5
17:63752108–63752109	acceptor_loss	1.0000	3
17:63752114–63752115	acceptor_gain	1.0000	2
17:63752739–63752740	donor_loss	1.0000	3
17:63752800–63752801	acceptor_loss	1.0000	5
17:63752805	acceptor_gain	1.0000
17:63756574	acceptor_gain	1.0000
17:63756582	acceptor_gain	1.0000
17:63760980–63760981	acceptor_loss	1.0000	5
17:63764922	acceptor_gain	1.0000

AlphaMissense

1,621 missense substitutions predicted likely pathogenic (of 3,268 scored), across 354 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
M475	9	0.869	0.992
N160	8	0.999	1.000
D229	8	0.997	0.999
D243	8	0.995	0.999
H422	8	0.994	1.000
D278	8	0.990	0.997
F39	8	0.989	0.999
F179	8	0.988	1.000
D335	8	0.988	0.997
D184	8	0.981	0.995
D449	8	0.981	0.998
F42	8	0.977	0.999
N152	8	0.955	0.999
D38	8	0.925	0.990
F224	8	0.925	0.996
H171	8	0.915	0.996
F363	8	0.881	0.997
D257	8	0.879	0.986
D314	8	0.860	0.982
F361	8	0.859	0.993

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	4.17e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.03e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000441
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000781

Disease associations

OMIM: gene MIM:618260 | disease phenotypes: MIM:618268

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
trichohepatoneurodevelopmental syndrome	Definitive	Autosomal recessive	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
DDG2P	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green

Mondo (1): trichohepatoneurodevelopmental syndrome (MONDO:0032645)

HPO phenotypes

showing 60 of 82 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000414	Bulbous nose
HP:0000483	Astigmatism
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000540	Hypermetropia
HP:0000656	Ectropion
HP:0000664	Synophrys
HP:0000678	Dental crowding
HP:0000687	Widely spaced teeth
HP:0000691	Microdontia
HP:0000767	Pectus excavatum
HP:0000774	Narrow chest
HP:0000821	Hypothyroidism
HP:0000989	Pruritus
HP:0001081	Cholelithiasis
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001357	Plagiocephaly
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001410	Decreased liver function
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001622	Premature birth
HP:0001629	Ventricular septal defect
HP:0001643	Patent ductus arteriosus
HP:0001738	Exocrine pancreatic insufficiency
HP:0001744	Splenomegaly
HP:0001762	Talipes equinovarus
HP:0001773	Short foot
HP:0001845	Overlapping toe
HP:0002020	Gastroesophageal reflux
HP:0002028	Chronic diarrhea
HP:0002059	Cerebral atrophy
HP:0002208	Coarse hair
HP:0002212	Curly hair
HP:0002224	Woolly hair
HP:0002240	Hepatomegaly
HP:0002353	EEG abnormality
HP:0002557	Hypoplastic nipples
HP:0002570	Steatorrhea
HP:0002650	Scoliosis
HP:0002714	Downturned corners of mouth
HP:0002719	Recurrent infections

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067137 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

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

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.87	Kd	136.3	nM	CHEMBL3752910
6.87	ED50	136.3	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148009: Binding affinity to human CCDC47 incubated for 45 mins by Kinobead based pull down assay	kd	0.1363	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	4
bisphenol A	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
aflatoxin B2	increases methylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Clozapine	increases expression, affects cotreatment	1
Coumestrol	increases expression	1
Cuprizone	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	increases reaction, affects binding	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Isoniazid	decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651051	Binding	Binding affinity to human CCDC47 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CCDC47 across ~30M SureChEMBL compounds — explore on Sugi Predict.