C6orf58

Summary

C6orf58 (chromosome 6 open reading frame 58, HGNC:20960) is a protein-coding gene on chromosome 6q22.33, encoding Protein LEG1 homolog (Q6P5S2). May be involved in early liver development.

Located in extracellular space.

Source: NCBI Gene 352999 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 12 total — 3 pathogenic
• MANE Select transcript: NM_001010905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20960
Approved symbol	C6orf58
Name	chromosome 6 open reading frame 58
Location	6q22.33
Locus type	gene with protein product
Status	Approved
Aliases	LEG1
Ensembl gene	ENSG00000184530
Ensembl biotype	protein_coding
OMIM	621149
Entrez	352999

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000329722, ENST00000498112

RefSeq mRNA: 1 — MANE Select: NM_001010905 NM_001010905

CCDS: CCDS34533

Canonical transcript exons

ENST00000329722 — 6 exons

Exon	Start	End
ENSE00001299640	127581182	127581282
ENSE00001314756	127590087	127590325
ENSE00001322484	127577174	127577486
ENSE00001326817	127580265	127580449
ENSE00001384530	127591543	127591820
ENSE00002516557	127578686	127578772

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 99.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.3685 / max 960.3078, expressed in 22 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69714	2.3685	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trachea	UBERON:0003126	99.74	gold quality
pylorus	UBERON:0001166	99.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.13	gold quality
minor salivary gland	UBERON:0001830	92.75	gold quality
nasal cavity mucosa	UBERON:0001826	91.32	gold quality
saliva-secreting gland	UBERON:0001044	87.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.25	gold quality
mouth mucosa	UBERON:0003729	86.70	gold quality
cardia of stomach	UBERON:0001162	84.19	gold quality
duodenum	UBERON:0002114	80.24	gold quality
pharyngeal mucosa	UBERON:0000355	77.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.99	gold quality
buccal mucosa cell	CL:0002336	67.90	silver quality
islet of Langerhans	UBERON:0000006	66.06	gold quality
right lung	UBERON:0002167	64.70	gold quality
tongue	UBERON:0001723	63.85	gold quality
fundus of stomach	UBERON:0001160	62.27	gold quality
stomach	UBERON:0000945	60.24	gold quality
left ovary	UBERON:0002119	59.91	gold quality
superior surface of tongue	UBERON:0007371	59.83	gold quality
right coronary artery	UBERON:0001625	59.79	gold quality
left uterine tube	UBERON:0001303	58.98	gold quality
body of stomach	UBERON:0001161	58.75	gold quality
endocervix	UBERON:0000458	58.68	gold quality
right uterine tube	UBERON:0001302	58.40	gold quality
right ovary	UBERON:0002118	58.03	gold quality
oral cavity	UBERON:0000167	56.95	gold quality
ovary	UBERON:0000992	55.74	gold quality
cortical plate	UBERON:0005343	55.48	gold quality
body of uterus	UBERON:0009853	55.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-11	no	39.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting C6orf58, 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-4775	99.98	75.00	6394
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-7161-3P	96.79	68.79	798
HSA-MIR-4444	92.67	67.92	56

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	C20H6orf58	ENSDARG00000090722
danio_rerio	C20H6orf58	ENSDARG00000095751
mus_musculus	2310057J18Rik	ENSMUSG00000015519
rattus_norvegicus	Leg1	ENSRNOG00000012581

Protein

Protein identifiers

Protein LEG1 homolog — Q6P5S2 (reviewed: Q6P5S2)

All UniProt accessions (1): Q6P5S2

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in early liver development.

Subcellular location. Secreted.

Tissue specificity. Detected in saliva and in hypomineralized dental enamel (at protein level).

Similarity. Belongs to the LEG1 family.

RefSeq proteins (1): NP_001010905* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008499	Leg1	Family

Pfam: PF05612

UniProt features (5 total): glycosylation site 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P5S2-F1	88.32	0.80

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 (2): 24, 69

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, DOUGLAS_BMI1_TARGETS_DN, SENESE_HDAC1_TARGETS_UP, chr6q22, HORIUCHI_WTAP_TARGETS_UP, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_DN, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA, RAO_BOUND_BY_SALL4_ISOFORM_A, ZWANG_EGF_INTERVAL_UP, YAP1_DN, ZSCAN21_TARGET_GENES, ZSCAN5C_TARGET_GENES, MIR335_3P, MIR551B_5P, MIR2115_3P

GO Biological Process (0):

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

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C6orf58	BPIFB1	Q8TDL5	641
C6orf58	MTCL3	Q5TF21	638
C6orf58	SPMIP1	A0A1B0GUX0	559
C6orf58	CA6	P23280	501
C6orf58	KIAA0408	Q6ZU52	461
C6orf58	CSTA	P01040	435
C6orf58	MMACHC	Q9Y4U1	428
C6orf58	CFAP61	Q8NHU2	419
C6orf58	CCDC127	Q96BQ5	417
C6orf58	ATAT1	Q5SQI0	411
C6orf58	RNF146	Q9NTX7	411
C6orf58	BPIFA2	Q96DR5	394
C6orf58	SPPL3	Q8TCT6	371
C6orf58	PTPRK	Q15262	365
C6orf58	TMED1	Q13445	363

IntAct

34 interactions, top by confidence:

A	B	Type	Score
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
ANXA1	LEG1	psi-mi:“MI:0915”(physical association)	0.560
CALR	LEG1	psi-mi:“MI:0915”(physical association)	0.560
LEG1	DLST	psi-mi:“MI:0915”(physical association)	0.560
LEG1	NEK7	psi-mi:“MI:0915”(physical association)	0.560
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
GKN1	CST4	psi-mi:“MI:0914”(association)	0.530
LEG1	LDLRAP1	psi-mi:“MI:0915”(physical association)	0.490
LDLRAP1	LEG1	psi-mi:“MI:0915”(physical association)	0.490
SNX27	IGLL5	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
STK11	A2ML1	psi-mi:“MI:0914”(association)	0.350
HBQ1	IGLL5	psi-mi:“MI:0914”(association)	0.350
COG2	CST4	psi-mi:“MI:0914”(association)	0.350
HINT2	CST4	psi-mi:“MI:0914”(association)	0.350
ITLN2	IGLC7	psi-mi:“MI:0914”(association)	0.350
SFXN4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
TIMM10	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), LDLRAP1 (Two-hybrid), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS), C6orf58 (Affinity Capture-MS)

ESM2 similar proteins: A0A345BJN9, A1XFV8, A3DRP6, A3RM21, A7WNB1, A8C8K0, B2ZCQ0, F5HDY6, P03499, P04858, P07051, P08593, P08671, P09280, P0C772, P0C773, P0CF75, P0DOE1, P13140, P14155, P21431, P22046, P31964, P47146, P52510, Q00151, Q04551, Q07458, Q07FH9, Q0GBY2, Q197F9, Q1I0U5, Q289M1, Q5K2K5, Q5NDN1, Q65YU7, Q6P5S2, Q6XSW4, Q6XTD8, Q6XTK0

Diamond homologs: A5PF61, Q4QRF7, Q5QT17, Q6P5S2, Q8C6C9, Q54KF5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1340790	GRCh37/hg19 6q22.31-22.33(chr6:125037475-129494795)x1	Pathogenic
1527284	GRCh37/hg19 6q22.31-22.33(chr6:122839432-128801386)	Pathogenic
58445	GRCh38/hg38 6q22.32-22.33(chr6:126255554-129431726)x1	Pathogenic

SpliceAI

893 predictions. Top by Δscore:

Variant	Effect	Δscore
6:127580374:G:GT	donor_gain	1.0000
6:127581180:A:AG	acceptor_gain	1.0000
6:127581181:G:GG	acceptor_gain	1.0000
6:127590086:GAT:G	acceptor_gain	1.0000
6:127580474:A:G	donor_gain	0.9900
6:127580478:G:GT	donor_gain	0.9900
6:127581181:GT:G	acceptor_gain	0.9900
6:127590083:TTA:T	acceptor_loss	0.9900
6:127590085:A:AG	acceptor_gain	0.9900
6:127590085:A:AT	acceptor_loss	0.9900
6:127590086:G:GG	acceptor_gain	0.9900
6:127590086:GATAT:G	acceptor_gain	0.9900
6:127590323:TAGG:T	donor_loss	0.9900
6:127590325:GGTAA:G	donor_loss	0.9900
6:127590326:G:C	donor_loss	0.9900
6:127590327:T:A	donor_loss	0.9900
6:127591540:CA:C	acceptor_loss	0.9900
6:127591541:A:AG	acceptor_gain	0.9900
6:127591542:G:GG	acceptor_gain	0.9900
6:127591542:G:GT	acceptor_loss	0.9900
6:127591542:GGTT:G	acceptor_gain	0.9900
6:127580374:G:T	donor_gain	0.9800
6:127590086:GATA:G	acceptor_gain	0.9800
6:127590086:GA:G	acceptor_gain	0.9700
6:127590326:G:GG	donor_gain	0.9700
6:127591538:TACAG:T	acceptor_gain	0.9700
6:127591539:ACAGG:A	acceptor_gain	0.9700
6:127577289:A:T	donor_gain	0.9500
6:127577328:GCAT:G	donor_gain	0.9500
6:127581181:GTA:G	acceptor_gain	0.9500

AlphaMissense

2179 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:127580432:T:A	W186R	0.983
6:127580432:T:C	W186R	0.983
6:127578760:A:C	S126R	0.981
6:127578762:T:A	S126R	0.981
6:127578762:T:G	S126R	0.981
6:127580378:T:C	F168L	0.977
6:127580380:T:A	F168L	0.977
6:127580380:T:G	F168L	0.977
6:127577440:T:A	N85K	0.971
6:127577440:T:G	N85K	0.971
6:127578690:A:C	R102S	0.970
6:127578690:A:T	R102S	0.970
6:127580434:G:C	W186C	0.969
6:127580434:G:T	W186C	0.969
6:127577369:G:T	G62W	0.966
6:127578766:T:A	W128R	0.955
6:127578766:T:C	W128R	0.955
6:127580303:G:C	A143P	0.954
6:127577284:G:C	W33C	0.952
6:127577284:G:T	W33C	0.952
6:127577350:G:C	W55C	0.952
6:127577350:G:T	W55C	0.952
6:127577348:T:A	W55R	0.950
6:127577348:T:C	W55R	0.950
6:127580300:G:C	A142P	0.949
6:127578689:G:C	R102T	0.948
6:127578768:G:C	W128C	0.947
6:127578768:G:T	W128C	0.947
6:127580295:T:C	F140S	0.945
6:127577365:A:C	R60S	0.943

dbSNP variants (sampled 300 via entrez): RS1000084952 (6:127581225 A>G), RS1000464340 (6:127576506 C>T), RS1000491701 (6:127584630 C>A,T), RS1000503280 (6:127578310 T>G), RS1000553179 (6:127576060 AGGATGTTTAATGT>A), RS1000773437 (6:127591491 A>C,G), RS1000959840 (6:127578595 T>C,G), RS1001067446 (6:127584654 G>A), RS1001187053 (6:127579435 T>C), RS1001197838 (6:127591750 A>G), RS1001310920 (6:127585927 A>G), RS1002210126 (6:127577207 G>A), RS1002287303 (6:127583520 A>G), RS1002338140 (6:127583698 C>T), RS1002606752 (6:127577015 T>G)

Disease associations

OMIM: gene MIM:621149 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003254_8	Urinary albumin-to-creatinine ratio in non-diabetics	3.000000e-06
GCST003944_9	Hepcidin/ferritin ratio	5.000000e-08
GCST008159_2	Waist-to-hip ratio adjusted for BMI	8.000000e-06
GCST009798_84	Asthma	3.000000e-10
GCST90020025_530	Waist-to-hip ratio adjusted for BMI	5.000000e-10
GCST90020025_531	Waist-to-hip ratio adjusted for BMI	6.000000e-09
GCST90020027_1050	Waist-hip index	2.000000e-10
GCST90020027_1051	Waist-hip index	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007778	urinary albumin to creatinine ratio
EFO:0007901	hepcidin:ferritin ratio
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
abrine	increases expression	1
Zoledronic Acid	increases expression	1
Aldehydes	increases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Demecolcine	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Silicon Dioxide	increases expression	1
Vincristine	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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