EVPLL

Summary

EVPLL (envoplakin like, HGNC:35236) is a protein-coding gene on chromosome 17p11.2, encoding Envoplakin-like protein (A8MZ36).

Predicted to be involved in intermediate filament cytoskeleton organization.

Source: NCBI Gene 645027 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 67 total — 1 pathogenic
• MANE Select transcript: NM_001145127

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35236
Approved symbol	EVPLL
Name	envoplakin like
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000214860
Ensembl biotype	protein_coding
Entrez	645027

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000399134, ENST00000583003, ENST00000883329, ENST00000968214, ENST00000968215, ENST00000968216

RefSeq mRNA: 1 — MANE Select: NM_001145127 NM_001145127

CCDS: CCDS45626

Canonical transcript exons

ENST00000399134 — 11 exons

Exon	Start	End
ENSE00001536610	18388857	18389647
ENSE00001536616	18383025	18383185
ENSE00001536621	18381603	18381730
ENSE00001536624	18380902	18381000
ENSE00001536625	18377778	18377983
ENSE00002351259	18381367	18381521
ENSE00002358974	18382513	18382638
ENSE00002363239	18383271	18383378
ENSE00002410328	18383492	18383587
ENSE00002413917	18382826	18382864
ENSE00003622836	18388219	18388288

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 93.19.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6080 / max 35.3522, expressed in 199 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159809	0.6080	199

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	93.19	gold quality
esophagus mucosa	UBERON:0002469	84.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.80	gold quality
skin of abdomen	UBERON:0001416	74.12	gold quality
zone of skin	UBERON:0000014	71.83	gold quality
vagina	UBERON:0000996	71.41	gold quality
skin of leg	UBERON:0001511	70.27	gold quality
right testis	UBERON:0004534	66.95	gold quality
right lobe of liver	UBERON:0001114	65.74	gold quality
testis	UBERON:0000473	63.42	gold quality
left testis	UBERON:0004533	62.54	gold quality
upper lobe of left lung	UBERON:0008952	62.12	gold quality
liver	UBERON:0002107	58.98	gold quality
right lung	UBERON:0002167	58.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	57.91	gold quality
lung	UBERON:0002048	57.70	gold quality
adult mammalian kidney	UBERON:0000082	57.09	gold quality
esophagus	UBERON:0001043	57.03	gold quality
thyroid gland	UBERON:0002046	56.99	gold quality
left lobe of thyroid gland	UBERON:0001120	56.68	gold quality
right lobe of thyroid gland	UBERON:0001119	55.45	gold quality
urinary bladder	UBERON:0001255	55.09	gold quality
mucosa of transverse colon	UBERON:0004991	54.23	gold quality
prostate gland	UBERON:0002367	53.89	gold quality
kidney	UBERON:0002113	53.70	gold quality
cortex of kidney	UBERON:0001225	51.77	gold quality
body of stomach	UBERON:0001161	51.47	gold quality
metanephros cortex	UBERON:0010533	50.40	gold quality
tonsil	UBERON:0002372	49.71	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting EVPLL, 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-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-558	97.50	67.16	977
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-6872-3P	97.08	66.99	750
HSA-MIR-3116	97.07	65.78	1324

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	evpla	ENSDARG00000019808
		ENSDARG00000103459

Paralogs (2): PPL (ENSG00000118898), EVPL (ENSG00000167880)

Protein

Protein identifiers

Envoplakin-like protein — A8MZ36 (reviewed: A8MZ36)

All UniProt accessions (1): A8MZ36

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the plakin or cytolinker family.

RefSeq proteins (1): NP_001138599* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043197	Plakin	Family
IPR055419	Spectrin_PEPL/EVPL	Domain

Pfam: PF23160

UniProt features (7 total): region of interest 2, compositionally biased region 2, chain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MZ36-F1	69.26	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 16 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, KMT2D_TARGET_GENES, SUPT16H_TARGET_GENES, UBN1_TARGET_GENES, MIR4490, MIR8077, MEBARKI_HCC_PROGENITOR_FZD8CRD_DN, DESCARTES_MAIN_FETAL_SQUAMOUS_EPITHELIAL_CELLS, DESCARTES_FETAL_KIDNEY_URETERIC_BUD_CELLS, GSE18791_CTRL_VS_NEWCASTLE_VIRUS_DC_12H_DN, LIU_OVARIAN_CANCER_TUMORS_AND_XENOGRAFTS_XDGS_UP, GOBP_CYTOSKELETON_ORGANIZATION, GSE21927_HEALTHY_VS_TUMOROUS_BALBC_MOUSE_MONOCYTE_DN, GSE25088_CTRL_VS_IL4_STIM_STAT6_KO_MACROPHAGE_DN

GO Biological Process (1): intermediate filament cytoskeleton organization (GO:0045104)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton organization	1
intermediate filament-based process	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EVPLL	SLFNL1	Q499Z3	572
EVPLL	NBPF4	Q96M43	533
EVPLL	CA11	O75493	451
EVPLL	TIMM29	Q9BSF4	380
EVPLL	LRRC37A	A6NMS7	368
EVPLL	LRRC37A3	O60309	360
EVPLL	EXOC6B	Q9Y2D4	356
EVPLL	C19orf18	Q8NEA5	348
EVPLL	DGCR6L	Q9BY27	336
EVPLL	KIAA0319L	Q8IZA0	330
EVPLL	TDRD5	Q8NAT2	317
EVPLL	OTUD7A	Q8TE49	313
EVPLL	RNF122	Q9H9V4	311
EVPLL	NSUN3	Q9H649	305
EVPLL	C11orf87	Q6NUJ2	301

IntAct

0 interactions, top by confidence:

BioGRID (2): EVPLL (Affinity Capture-MS), EVPLL (Affinity Capture-MS)

ESM2 similar proteins: A6NC78, A6NCC3, A6NEM1, A6NJZ7, A6NMD2, A6NN73, A6NNM3, A7E2F4, A8E4N3, A8MQT2, A8MZ36, F8WBI6, H3BPF8, H3BQL2, H3BV12, I6L899, O76081, P05433, P0C7N4, P0CJ92, P0DX52, P0DX53, P54257, P57679, P57680, Q0D2H9, Q3TES0, Q3UPH7, Q3V0F0, Q4FZC9, Q5JYT7, Q6GQV0, Q6NSJ2, Q6QZQ4, Q6ZMZ3, Q76M68, Q7TSF4, Q80TT8, Q80UW3, Q86UK5

Diamond homologs: A8MZ36, Q92817, Q9D952, A0A8M2BID5, A0A8M9PQ61, E9Q557, F1LMV6, O60437, Q9R269

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	61
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
980120	GRCh37/hg19 17p12-11.2(chr17:15810015-18537436)x1	Pathogenic

SpliceAI

1509 predictions. Top by Δscore:

Variant	Effect	Δscore
17:18377980:GCTG:G	donor_gain	1.0000
17:18380892:A:AG	acceptor_gain	1.0000
17:18380893:C:G	acceptor_gain	1.0000
17:18380900:A:G	acceptor_gain	1.0000
17:18380938:A:AG	acceptor_gain	1.0000
17:18380938:AT:A	acceptor_gain	1.0000
17:18380939:T:G	acceptor_gain	1.0000
17:18380943:A:G	acceptor_gain	1.0000
17:18380997:GCAG:G	donor_gain	1.0000
17:18380999:AGG:A	donor_loss	1.0000
17:18381001:G:GG	donor_gain	1.0000
17:18381001:GT:G	donor_loss	1.0000
17:18381002:T:G	donor_loss	1.0000
17:18381364:CA:C	acceptor_loss	1.0000
17:18381365:A:AG	acceptor_gain	1.0000
17:18381366:G:GT	acceptor_gain	1.0000
17:18381366:GGA:G	acceptor_gain	1.0000
17:18381366:GGAC:G	acceptor_gain	1.0000
17:18381366:GGACC:G	acceptor_gain	1.0000
17:18381502:GC:G	donor_gain	1.0000
17:18381503:C:G	donor_gain	1.0000
17:18381508:GAGAC:G	donor_gain	1.0000
17:18381516:G:GT	donor_gain	1.0000
17:18381517:AAGGA:A	donor_gain	1.0000
17:18381518:AGGA:A	donor_gain	1.0000
17:18381519:G:GT	donor_gain	1.0000
17:18381519:GGA:G	donor_gain	1.0000
17:18381519:GGAG:G	donor_loss	1.0000
17:18381520:G:GT	donor_gain	1.0000
17:18381520:GA:G	donor_gain	1.0000

AlphaMissense

1953 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:18383528:T:C	F273L	0.946
17:18383530:C:A	F273L	0.946
17:18383530:C:G	F273L	0.946
17:18383521:G:C	W270C	0.945
17:18383521:G:T	W270C	0.945
17:18383279:G:C	K227N	0.937
17:18383279:G:T	K227N	0.937
17:18383519:T:A	W270R	0.924
17:18383519:T:C	W270R	0.924
17:18383140:G:C	W209C	0.901
17:18383140:G:T	W209C	0.901
17:18383138:T:A	W209R	0.900
17:18383138:T:C	W209R	0.900
17:18383124:T:C	I204T	0.876
17:18381460:T:C	F53L	0.867
17:18381462:C:A	F53L	0.867
17:18381462:C:G	F53L	0.867
17:18383529:T:C	F273S	0.867
17:18383520:G:C	W270S	0.846
17:18383544:T:C	I278T	0.846
17:18383303:G:C	E235D	0.842
17:18383303:G:T	E235D	0.842
17:18383180:T:C	Y223H	0.837
17:18383538:T:C	L276P	0.829
17:18383551:G:C	Q280H	0.824
17:18383551:G:T	Q280H	0.824
17:18383529:T:G	F273C	0.816
17:18383532:T:C	L274P	0.807
17:18383274:T:C	F226L	0.797
17:18383276:C:A	F226L	0.797

dbSNP variants (sampled 300 via entrez): RS1000232604 (17:18383492 G>A), RS1000267659 (17:18377868 G>A), RS1000569900 (17:18382310 T>G), RS1000743513 (17:18378111 G>A,T), RS1000981293 (17:18384537 C>T), RS1000997399 (17:18376667 AG>A,AGG), RS1001542391 (17:18388724 G>T), RS1001591920 (17:18382592 A>C,G), RS1001903935 (17:18387434 C>T), RS1001928963 (17:18381375 G>A,T), RS1001970310 (17:18389112 C>A,T), RS1002277757 (17:18387227 T>C), RS1002502136 (17:18376452 G>C), RS1002858401 (17:18376617 C>A), RS1002991377 (17:18384504 T>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:240500, MIM:213300, MIM:249000

GenCC curated gene-disease

Mondo (3): immunodeficiency, common variable, 2 (MONDO:0009413), Joubert syndrome (MONDO:0018772), Meckel syndrome (MONDO:0018921)

Orphanet (3): OBSOLETE: Common variable immunodeficiency (Orphanet:1572), Isolated Joubert syndrome (Orphanet:475), Meckel syndrome (Orphanet:564)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
Estradiol	affects expression, decreases expression	2
Cadmium Chloride	decreases expression	2
bisphenol A	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
Acetaminophen	decreases expression	1
Nicotine	increases expression	1
Thiram	increases expression	1
Gold Compounds	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)