ECPAS

Summary

ECPAS (Ecm29 proteasome adaptor and scaffold, HGNC:29020) is a protein-coding gene on chromosome 9q31.3, encoding Proteasome adapter and scaffold protein ECM29 (Q5VYK3). Adapter/scaffolding protein that binds to the 26S proteasome, motor proteins and other compartment specific proteins.

Enables proteasome binding activity. Involved in ERAD pathway. Located in several cellular components, including centrosome; cytoplasmic vesicle; and nucleoplasm.

Source: NCBI Gene 23392 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 369 total (top 9% of genes corpus-wide)
• GTEx eGene: eQTL in 18 tissues, sQTL in 3 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.32 (highly constrained)
• MANE Select transcript: NM_001364929
• Notable: 369 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29020
Approved symbol	ECPAS
Name	Ecm29 proteasome adaptor and scaffold
Location	9q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22036, ECM29
Ensembl gene	ENSG00000136813
Ensembl biotype	protein_coding
OMIM	616694
Entrez	23392

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 17 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000684092

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

ENST00000684092, ENST00000259335, ENST00000338205, ENST00000374383, ENST00000465499, ENST00000602447, ENST00000602978, ENST00000855863, ENST00000855864, ENST00000932780, ENST00000932781, ENST00000932782, ENST00000967701, ENST00000967702, ENST00000967703, ENST00001044580, ENST00001107987, ENST00001107988, ENST00001137165

RefSeq mRNA: 4 — MANE Select: NM_001364929 NM_001363756, NM_001364929, NM_001364930, NM_001364931

CCDS: CCDS87673, CCDS94456

Canonical transcript exons

ENST00000684092 — 50 exons

Exon	Start	End
ENSE00000720073	111363588	111363659
ENSE00000720075	111366239	111366327
ENSE00000720082	111370435	111370627
ENSE00000720085	111370722	111370765
ENSE00000720190	111420017	111420120
ENSE00000720194	111421921	111422043
ENSE00000720197	111422134	111422200
ENSE00000806117	111417883	111418006
ENSE00000806118	111423199	111423248
ENSE00001364494	111442306	111442424
ENSE00001367049	111430547	111430628
ENSE00001368357	111451425	111451555
ENSE00001369993	111444378	111444494
ENSE00001376162	111440372	111440521
ENSE00001383492	111433233	111433372
ENSE00001383777	111436940	111437108
ENSE00001389082	111428042	111428161
ENSE00001419591	111425418	111425496
ENSE00001423748	111425743	111425828
ENSE00001463465	111472897	111473000
ENSE00001630230	111412014	111412148
ENSE00001743907	111413895	111413986
ENSE00001749591	111410041	111410213
ENSE00001750168	111410980	111411142
ENSE00001768316	111414429	111414651
ENSE00001790887	111416272	111416352
ENSE00003469777	111369035	111369173
ENSE00003473072	111389556	111389723
ENSE00003478420	111373170	111373236
ENSE00003500191	111394160	111394305
ENSE00003537610	111373315	111373406
ENSE00003547721	111366522	111366627
ENSE00003554775	111397030	111397153
ENSE00003557551	111392768	111392882
ENSE00003585514	111391756	111391824
ENSE00003609697	111389984	111390101
ENSE00003610260	111385337	111385442
ENSE00003611311	111378580	111378730
ENSE00003618161	111371621	111371829
ENSE00003636511	111384522	111384569
ENSE00003637896	111375113	111375202
ENSE00003640171	111393680	111393734
ENSE00003641180	111386377	111386456
ENSE00003656577	111376476	111376541
ENSE00003664642	111372429	111372620
ENSE00003680110	111373972	111374038
ENSE00003686389	111383211	111383332
ENSE00003785668	111408571	111408672
ENSE00003920599	111484116	111484383
ENSE00003920851	111360685	111362169

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.0410 / max 307.7590, expressed in 1825 samples.

Highest expression (Bgee): gastrocnemius, tendon of biceps brachii, buccal mucosa cell, muscle of leg, hindlimb stylopod muscle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ECPAS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 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 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Spinal cord cervical c-1	eqtl	3.8e-20	+0.63	9:111335011:G:C
Testis	eqtl	4.4e-10	+0.20	9:111452720:C:T
Brain Hypothalamus	eqtl	1.6e-07	+0.25	9:111432603:G:A
Cells Cultured fibroblasts	sqtl	2.0e-06	-0.97	9:111403341:C:T
Brain Substantia nigra	eqtl	6.9e-06	+0.32	9:111386216:A:G
Cells Cultured fibroblasts	eqtl	2.2e-05	+0.42	9:111217956:T:C
Skin Not Sun Exposed Suprapubic	eqtl	4.7e-04	+0.12	9:111458323:C:T
Brain Putamen basal ganglia	eqtl	7.8e-04	+0.16	9:111439523:C:G
Brain Caudate basal ganglia	eqtl	1.3e-03	+0.11	9:111411868:C:T
Colon Transverse	eqtl	1.9e-03	+0.67	9:110850479:T:C
Skin Sun Exposed Lower leg	eqtl	9.3e-03	+0.09	9:111458323:C:T
Muscle Skeletal	sqtl	1.4e-02	-0.23	9:111456667:G:A
Adrenal Gland	eqtl	2.0e-02	+1.34	9:112147375:G:A
Esophagus Muscularis	eqtl	2.1e-02	-0.11	9:111410883:C:A
Cells EBV-transformed lymphocytes	sqtl	3.1e-02	-1.05	9:111367194:G:C
Brain Cerebellum	eqtl	3.2e-02	-0.53	9:111337407:T:C
Esophagus Mucosa	eqtl	3.4e-02	+0.21	9:111488579:C:T
Cells EBV-transformed lymphocytes	eqtl	3.4e-02	-0.40	9:111931170:C:A
Brain Nucleus accumbens basal ganglia	eqtl	3.5e-02	+0.10	9:111468195:G:C
Heart Atrial Appendage	eqtl	4.5e-02	-0.07	9:112038560:T:C

FANTOM5 promoters

showing 10 of 15 alternative TSS:

Promoter ID	TPM avg	Samples expressed
102013	29.0780	1813
101997	8.4150	1711
102014	6.1124	1725
102005	4.3598	1582
102006	0.8713	590
102004	0.7701	396
101999	0.6132	314
102008	0.5733	337
102007	0.3118	118
101998	0.2593	101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.54	gold quality
tendon of biceps brachii	UBERON:0008188	98.30	gold quality
buccal mucosa cell	CL:0002336	98.26	gold quality
muscle of leg	UBERON:0001383	98.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.24	gold quality
gluteal muscle	UBERON:0002000	98.09	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.93	gold quality
skeletal muscle tissue	UBERON:0001134	97.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.54	gold quality
muscle organ	UBERON:0001630	97.50	gold quality
skeletal muscle organ	UBERON:0014892	97.50	gold quality
deltoid	UBERON:0001476	97.44	gold quality
biceps brachii	UBERON:0001507	97.38	gold quality
medial globus pallidus	UBERON:0002477	97.31	gold quality
endothelial cell	CL:0000115	97.02	gold quality
body of tongue	UBERON:0011876	97.01	gold quality
globus pallidus	UBERON:0001875	96.99	gold quality
substantia nigra pars compacta	UBERON:0001965	96.93	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.93	gold quality
sperm	CL:0000019	96.77	gold quality
tibialis anterior	UBERON:0001385	96.77	gold quality
triceps brachii	UBERON:0001509	96.67	gold quality
lateral globus pallidus	UBERON:0002476	96.61	gold quality
male germ cell	CL:0000015	96.55	gold quality
muscle tissue	UBERON:0002385	96.55	gold quality
epithelium of nasopharynx	UBERON:0001951	96.39	gold quality
tendon	UBERON:0000043	96.33	gold quality
tongue	UBERON:0001723	96.30	gold quality
stromal cell of endometrium	CL:0002255	96.20	gold quality
diaphragm	UBERON:0001103	96.16	gold quality
germinal epithelium of ovary	UBERON:0001304	96.13	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.08	gold quality
tongue squamous epithelium	UBERON:0006919	95.98	gold quality
cartilage tissue	UBERON:0002418	95.94	gold quality
CA1 field of hippocampus	UBERON:0003881	95.94	gold quality
nucleus accumbens	UBERON:0001882	95.91	gold quality
cardia of stomach	UBERON:0001162	95.83	gold quality
putamen	UBERON:0001874	95.83	gold quality
pylorus	UBERON:0001166	95.73	gold quality
parotid gland	UBERON:0001831	95.67	gold quality
synovial joint	UBERON:0002217	95.65	gold quality
penis	UBERON:0000989	95.64	gold quality
caudate nucleus	UBERON:0001873	95.61	gold quality
urethra	UBERON:0000057	95.47	gold quality
colonic epithelium	UBERON:0000397	95.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.40	gold quality
adenohypophysis	UBERON:0002196	95.40	gold quality
trigeminal ganglion	UBERON:0001675	95.39	gold quality
hair follicle	UBERON:0002073	95.38	gold quality
body of pancreas	UBERON:0001150	95.30	gold quality
calcaneal tendon	UBERON:0003701	95.29	gold quality
nerve	UBERON:0001021	95.27	gold quality
tibial nerve	UBERON:0001323	95.27	gold quality
adrenal tissue	UBERON:0018303	95.27	gold quality
vagina	UBERON:0000996	95.24	gold quality
superior surface of tongue	UBERON:0007371	95.10	gold quality
parietal pleura	UBERON:0002400	95.04	gold quality
saphenous vein	UBERON:0007318	94.95	gold quality
renal medulla	UBERON:0000362	94.94	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.93	gold quality
pituitary gland	UBERON:0000007	94.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.80	gold quality
lower esophagus	UBERON:0013473	94.78	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.76	gold quality
islet of Langerhans	UBERON:0000006	94.69	gold quality
gingival epithelium	UBERON:0001949	94.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.69	gold quality
mucosa of stomach	UBERON:0001199	94.66	gold quality
adipose tissue	UBERON:0001013	94.65	gold quality
connective tissue	UBERON:0002384	94.64	gold quality
peritoneum	UBERON:0002358	94.63	gold quality
omental fat pad	UBERON:0010414	94.63	gold quality
pancreas	UBERON:0001264	94.62	gold quality
left ovary	UBERON:0002119	94.62	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.62	gold quality
body of uterus	UBERON:0009853	94.59	gold quality
right adrenal gland cortex	UBERON:0035827	94.59	gold quality
ovary	UBERON:0000992	94.58	gold quality
popliteal artery	UBERON:0002250	94.58	gold quality
blood vessel layer	UBERON:0004797	94.58	gold quality
tibial artery	UBERON:0007610	94.58	gold quality
oviduct epithelium	UBERON:0004804	94.57	gold quality
pleura	UBERON:0000977	94.56	gold quality
cervix squamous epithelium	UBERON:0006922	94.54	gold quality
endocervix	UBERON:0000458	94.53	gold quality
primary visual cortex	UBERON:0002436	94.52	gold quality
cardiac ventricle	UBERON:0002082	94.50	gold quality
jejunum	UBERON:0002115	94.50	gold quality
right ovary	UBERON:0002118	94.50	gold quality
minor salivary gland	UBERON:0001830	94.49	gold quality
heart right ventricle	UBERON:0002080	94.49	gold quality
heart left ventricle	UBERON:0002084	94.49	gold quality
Ammon’s horn	UBERON:0001954	94.48	gold quality
skin of leg	UBERON:0001511	94.47	gold quality
prostate gland	UBERON:0002367	94.46	gold quality
mouth mucosa	UBERON:0003729	94.45	gold quality
pharyngeal mucosa	UBERON:0000355	94.42	gold quality
right frontal lobe	UBERON:0002810	94.41	gold quality
skin of abdomen	UBERON:0001416	94.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.38
E-MTAB-6142	no	132.30

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	135.3	not detected
Nucleus accumbens	tissue	89.7
Tongue	tissue	83.8
Hippocampus	tissue	79.4	not detected
Postcentral gyrus	tissue	76.9
Locus coeruleus	tissue	72.0
Choroid plexus	tissue	66.4
Putamen	tissue	54.2
Cerebral cortex	tissue	47.7	not detected
Somatosensory cortex	tissue	47.7
Basal ganglia	tissue	46.8	not detected
Occipital cortex	tissue	45.5
Pons	tissue	44.5
Motor cortex	tissue	44.2
Superior colliculi	tissue	43.0
Thalamus	tissue	42.6
Ventral forebrain	tissue	42.3
Prefrontal cortex	tissue	42.2
Hippocampal formation	tissue	41.2
Spinal cord	tissue	41.1
Retrosplenial and cingulate cortex	tissue	41.0
Midbrain	tissue	40.8
Entorhinal cortex	tissue	40.0
Temporal cortex	tissue	39.8
Retrosplenial cortex	tissue	39.6
Medulla oblongata	tissue	38.9
Substantia nigra	tissue	38.4
Insular cortex	tissue	37.6
Hypothalamus	tissue	36.3
Septum	tissue	36.2
Adipose tissue	tissue	36.0	medium
Parathyroid gland	tissue	35.6	not detected
Cerebellum	tissue	35.0	not detected
Periaqueductal gray	tissue	33.9
Amygdala	tissue	33.4
Olfactory bulb	tissue	33.0
Corpus callosum	tissue	32.4
Pituitary gland	tissue	31.4
Prostate	tissue	29.8	low
Vagina	tissue	29.3	not detected
Duodenum	tissue	28.7	medium
Testis	tissue	28.6	medium
Colon	tissue	27.3	low
Adrenal gland	tissue	27.2	low
Thyroid gland	tissue	26.9	medium
Caudate putamen	tissue	26.7
Stomach 1	tissue	26.1	high
Small intestine	tissue	26.0	low
Rectum	tissue	25.7	not detected
Skin 1	tissue	25.6	not detected
Breast	tissue	25.6	low
Bone marrow	tissue	25.5	not detected
Frontal cortex	tissue	25.2
Ovary	tissue	25.1	medium
Pancreas	tissue	25.0	high
Heart muscle	tissue	24.9	not detected
Retina	tissue	24.6
Kidney	tissue	24.3	medium
Liver	tissue	23.9	medium
Smooth muscle	tissue	23.8	not detected

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Hippocampus, CA3 (106.7), Hippocampus, CA1 (99.0), Orbitofrontal gyrus, anterior (95.4), Posterior cingulate cortex (95.0), Hippocampus, CA2 (81.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 75 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.316, missense Z 2.72 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000684092 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
9:111,362,033–111,410,055	960 / 1179.0	0.81	no
9:111,410,056–111,412,085	194 / 152.8	1.27	no
9:111,412,086–111,440,521	573 / 716.2	0.80	no
9:111,442,306–111,472,918	90 / 158.5	0.57	no

Literature-anchored findings (GeneRIF, showing 5)

• Ecm29 protein serves to couple the 26 S proteasome to secretory compartments engaged in quality control and to other sites of enhanced proteolysis (PMID:15496406)
• Ecm29 serves as an adaptor for coupling 26 S proteasomes to specific cellular compartments. (PMID:20682791)
• The absence of Ecm29 enhanced TLR3 signaling, which was characterized by the increased abundance of the adaptor protein and E3 ubiquitin ligase tumor necrosis factor receptor-associated factor 3 (PMID:24084648)
• Ecm29 is involved in the dissociation process of 26S proteasome, providing clue to analyse the mechanism of proteasomal degradation under various stress condition. (PMID:26802743)
• Data suggest that the adapter protein ECM29 is the main proteasome-interacting protein responsible for oxidative stress-induced proteasome disassembly/remodeling; ECM29 appears to intrude on interaction between the 20S core particle and 19S regulatory particle in 26S proteasome, disrupting proteasome structure in response to oxidative stress. (PMID:28821611)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ecpas	ENSDARG00000061952
mus_musculus	Ecpas	ENSMUSG00000050812
rattus_norvegicus	Ecpas	ENSRNOG00000025076
drosophila_melanogaster	CG8858	FBGN0033698
caenorhabditis_elegans		WBGENE00008422

Paralogs (1): GCN1 (ENSG00000089154)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2140220) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
hyperactivity	1
abnormal vocalization	1
increased circulating phosphate level	1
abnormal coat/hair pigmentation	1
abnormal neuron morphology	1
increased susceptibility to pharmacologically induced seizures	1
abnormal GABA-mediated receptor currents	1
abnormal behavior	1
abnormal axon initial segment morphology	1
abnormal GABAergic neuron physiology	1
decreased thigmotaxis	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	Q5R6J0	99.4%	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
ZNF483	protein-coding	158399
PTGR1	protein-coding	22949
OR2K2	protein-coding	26248
MIR7702	ncRNA	102465800
DNAJC25	protein-coding	548645
DNAJC25-GNG10	protein-coding	552891

Protein

Protein identifiers

Proteasome adapter and scaffold protein ECM29 — Q5VYK3 (reviewed: Q5VYK3)

Alternative names: Ecm29 proteasome adapter and scaffold, Proteasome-associated protein ECM29 homolog

All UniProt accessions (6): A0AAA9X0G7, F6XAQ5, J3KN16, Q5VYK3, R4GMY1, R4GMY3

UniProt curated annotations — full annotation on UniProt →

Function. Adapter/scaffolding protein that binds to the 26S proteasome, motor proteins and other compartment specific proteins. May couple the proteasome to different compartments including endosome, endoplasmic reticulum and centrosome. May play a role in ERAD and other enhanced proteolysis. Promotes proteasome dissociation under oxidative stress.

Subunit / interactions. Non-stoichiometric component of the proteasome; associates with the 26S proteasome. Interacts (via N-terminus) with VPS11, VPS26A, VPS36, RAB11FIP4 and RABEP1. Interacts (via C-terminus) with DCTN1, DCTN2, KIF5B, MYH7, MYH10, MYO10 and ARF6.

Subcellular location. Endoplasmic reticulum. Endoplasmic reticulum-Golgi intermediate compartment. Endosome. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Nucleus. Multivesicular body. Cytoplasmic vesicle.

Similarity. Belongs to the ECM29 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VYK3-1	1	yes
Q5VYK3-2	2

RefSeq proteins (4): NP_001350685, NP_001351858, NP_001351859, NP_001351860 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR024372	Ecm29_N	Domain
IPR055443	HEAT_ECM29	Domain
IPR055444	ARM_ECM29	Domain

Pfam: PF12755, PF13001, PF23702, PF23731, PF24492

UniProt features (38 total): repeat 27, modified residue 3, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, cross-link 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VYK3-F1	84.03	0.40

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH uncertain · IF supported

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 (4)

Type	Positions
N-acetylalanine	2
Phosphoserine	830
Phosphothreonine	836
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	1039

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: 135 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_151, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEASOME_ASSEMBLY, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_TRANS_GOLGI_NETWORK, GOCC_COATED_VESICLE, GOCC_CENTROSOME, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, CUI_TCF21_TARGETS_2_DN, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, HAN_SATB1_TARGETS_DN, GOBP_ERAD_PATHWAY, GOBP_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (2): ERAD pathway (GO:0036503), proteasome assembly (GO:0043248)

GO Molecular Function (3): molecular adaptor activity (GO:0060090), proteasome binding (GO:0070628), protein binding (GO:0005515)

GO Cellular Component (15): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), early endosome (GO:0005769), late endosome (GO:0005770), multivesicular body (GO:0005771), endoplasmic reticulum (GO:0005783), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), centrosome (GO:0005813), membrane (GO:0016020), COPII-coated ER to Golgi transport vesicle (GO:0030134), endocytic vesicle (GO:0030139), cytoplasmic vesicle (GO:0031410), endosome (GO:0005768)

GO top-level categories

22 GO namespaces:

Category	Terms
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
cytoplasm	3
binding	2
endosome	2
endomembrane system	2
cytoplasmic vesicle	2
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
protein-containing complex assembly	1
molecular_function	1
protein-containing complex binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
nuclear lumen	1
intracellular anatomical structure	1
late endosome	1
centriole	1
microtubule organizing center	1
coated vesicle	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
ERAD pathway	BP	mutant phenotype
COPII-coated ER to Golgi transport vesicle	CC	direct assay
centrosome	CC	direct assay
cytoplasmic vesicle	CC	direct assay
early endosome	CC	direct assay
endocytic vesicle	CC	direct assay
endoplasmic reticulum	CC	direct assay
late endosome	CC	direct assay
membrane	CC	high-throughput assay
multivesicular body	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
proteasome binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,146 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECPAS	PSME4	Q14997	715
ECPAS	POMP	Q9Y244	684
ECPAS	PSMD14	O00487	596
ECPAS	PSMD4	P55036	585
ECPAS	CADPS2	Q86UW7	570
ECPAS	USP14	P54578	561
ECPAS	ADRM1	Q16186	557
ECPAS	PSMF1	Q92530	550
ECPAS	PAAF1	Q9BRP4	534
ECPAS	PSMC4	P43686	525
ECPAS	PSME3	P61289	501
ECPAS	CNOT4	O95628	494
ECPAS	PSMD8	P48556	491
ECPAS	PSMD12	O00232	485
ECPAS	PSMD10	O75832	459

IntAct

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

15 partners by confidence:

Partner	Interaction type	MIscore	Records
AGTRAP	physical association	0.560	6
CMTM5	physical association	0.560	6
MAL2	physical association	0.560	5
BSND	physical association	0.560	3
CMTM6	physical association	0.560	3
DGAT2L6	physical association	0.560	3
HSD17B13	physical association	0.560	3
TNFRSF10D	physical association	0.560	3
TMEM267	association	0.530	2
HSPB1	physical association	0.370	1
PCM1	physical association	0.370	1
PSMD1	association	0.350	2
CYP2J2	association	0.350	1
IKBKG	physical association	0.000	1
PTP4A3	physical association	0.000	1

Disease & clinical

Genetic variants

Variant evidence for ECPAS: 369 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	301
Likely benign	8
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 4,320):

Position(s)	Effect	Δscore	Sites
9:111366237–111366238	donor_loss	1.0000	5
9:111366328–111366329	acceptor_loss	1.0000	3
9:111366339	acceptor_gain	1.0000
9:111369033–111369034	donor_loss	1.0000	5
9:111369175	acceptor_loss	1.0000	2
9:111369179–111369181	acceptor_gain	1.0000	2
9:111369186	acceptor_gain	1.0000
9:111370433–111370434	donor_loss	1.0000	5
9:111370638–111370639	acceptor_gain	1.0000	2
9:111371619–111371620	donor_loss	1.0000	5

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.09e-08

Disease associations

OMIM: gene MIM:616694 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST90002387_103	Immature fraction of reticulocytes	1e-9
GCST003994_3	Age at voice drop	1e-7
GCST004750_72	Squamous cell lung carcinoma	5e-6
GCST009391_691	Metabolite levels	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007888	age at voice drop
EFO:0008529	kynurenine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295853 (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
5.94	Kd	1151	nM	CHEMBL5653589
5.94	ED50	1151	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148282: Binding affinity to human ECM29 incubated for 45 mins by Kinobead based pull down assay	kd	1.1505	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	9
bisphenol A	affects expression, decreases expression, increases expression	3
trichostatin A	affects expression, decreases expression, increases expression	2
entinostat	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation, increases ADP-ribosylation	1
2-palmitoylglycerol	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119005	Binding	Binding affinity to KIAA0368 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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