LCA5L

Summary

LCA5L (lebercilin LCA5 like, HGNC:1255) is a protein-coding gene on chromosome 21q22.2, encoding Lebercilin-like protein (O95447).

Predicted to be involved in intraciliary transport. Predicted to be active in axoneme.

Source: NCBI Gene 150082 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_152505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1255
Approved symbol	LCA5L
Name	lebercilin LCA5 like
Location	21q22.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC33295
Ensembl gene	ENSG00000157578
Ensembl biotype	protein_coding
Entrez	150082

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000288350, ENST00000358268, ENST00000380671, ENST00000411566, ENST00000415863, ENST00000418018, ENST00000426783, ENST00000434281, ENST00000438404, ENST00000448288, ENST00000451131, ENST00000456017, ENST00000459939, ENST00000466954, ENST00000468009, ENST00000480612, ENST00000484878, ENST00000485895, ENST00000490184, ENST00000491625, ENST00000495240, ENST00000855513, ENST00000951471

RefSeq mRNA: 22 — MANE Select: NM_152505 NM_001384285, NM_001384286, NM_001384287, NM_001384288, NM_001384289, NM_001384291, NM_001384292, NM_001384293, NM_001384294, NM_001384295, NM_001384296, NM_001384297, NM_001384298, NM_001384299, NM_001384300, NM_001384301, NM_001384302, NM_001384304, NM_001384308, NM_001384310, NM_001384313, NM_152505

CCDS: CCDS13665, CCDS93098

Canonical transcript exons

ENST00000288350 — 11 exons

Exon	Start	End
ENSE00001033593	39422976	39423490
ENSE00001367319	39429131	39429211
ENSE00001380142	39444135	39444201
ENSE00001391688	39435420	39435573
ENSE00001643940	39445725	39445778
ENSE00003491574	39411718	39411802
ENSE00003503789	39420706	39420843
ENSE00003604959	39410264	39410367
ENSE00003608880	39409979	39410096
ENSE00003787481	39428172	39428503
ENSE00003913818	39405728	39406612

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 96.80.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3821 / max 86.6083, expressed in 673 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190502	1.3821	673

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.80	gold quality
right testis	UBERON:0004534	96.30	gold quality
sperm	CL:0000019	95.37	gold quality
testis	UBERON:0000473	94.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.21	gold quality
buccal mucosa cell	CL:0002336	90.53	gold quality
bronchial epithelial cell	CL:0002328	89.42	gold quality
right uterine tube	UBERON:0001302	89.02	gold quality
adult organism	UBERON:0007023	88.10	gold quality
bronchus	UBERON:0002185	87.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.53	gold quality
tibialis anterior	UBERON:0001385	76.33	silver quality
gastrocnemius	UBERON:0001388	76.14	gold quality
muscle of leg	UBERON:0001383	75.80	gold quality
calcaneal tendon	UBERON:0003701	75.57	gold quality
adrenal tissue	UBERON:0018303	74.68	gold quality
fallopian tube	UBERON:0003889	74.56	gold quality
islet of Langerhans	UBERON:0000006	74.34	gold quality
left adrenal gland	UBERON:0001234	73.45	gold quality
left adrenal gland cortex	UBERON:0035825	73.25	gold quality
epithelium of nasopharynx	UBERON:0001951	73.13	silver quality
nasopharynx	UBERON:0001728	73.12	silver quality
hindlimb stylopod muscle	UBERON:0004252	72.89	gold quality
right adrenal gland	UBERON:0001233	72.85	gold quality
right lobe of thyroid gland	UBERON:0001119	72.80	gold quality
skeletal muscle organ	UBERON:0014892	72.63	gold quality
left lobe of thyroid gland	UBERON:0001120	72.44	gold quality
right adrenal gland cortex	UBERON:0035827	72.43	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.52
E-ANND-3	yes	6.16
E-GEOD-124858	no	113.91

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• RNA-seq evidence of biallelic expression of LCA5L and 10 neighboring genes in at least one primary human tissue tested indicates that the expression of LCA5L is uncoupled from the control of the maternally inherited 5mCpG imprints at the WRB differentially methylated region (DMR) in disomic controls or trisomy (Down syndrome) individuals. (PMID:27100087)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lca5l	ENSMUSG00000045275
rattus_norvegicus	Lca5l	ENSRNOG00000028248
drosophila_melanogaster	CG6652	FBGN0036687

Paralogs (1): LCA5 (ENSG00000135338)

Protein

Protein identifiers

Lebercilin-like protein — O95447 (reviewed: O95447)

Alternative names: Leber congenital amaurosis 5-like protein

All UniProt accessions (11): O95447, A0A1D5RMP5, C9J198, C9J293, C9J5D2, C9J9Z3, C9JFB6, C9JIJ8, C9JRD7, C9JYR0, U3KPS7

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the LCA5 family.

RefSeq proteins (21): NP_001371214, NP_001371215, NP_001371216, NP_001371217, NP_001371218, NP_001371220, NP_001371221, NP_001371222, NP_001371223, NP_001371224, NP_001371225, NP_001371226, NP_001371227, NP_001371228, NP_001371229, NP_001371230, NP_001371231, NP_001371233, NP_001371239, NP_001371242, NP_689718* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026188	Lebercilin-like	Family
IPR028933	Lebercilin_dom	Domain

Pfam: PF15619

UniProt features (15 total): region of interest 5, compositionally biased region 4, coiled-coil region 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95447-F1	62.76	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): WANG_LMO4_TARGETS_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CELL_PROJECTION_ORGANIZATION, chr21q22, BIDUS_METASTASIS_UP, GOCC_CYTOPLASMIC_REGION, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CERIBELLI_GENES_INACTIVE_AND_BOUND_BY_NFY, GOBP_INTRACILIARY_TRANSPORT, GOBP_INTRACELLULAR_TRANSPORT, YAP1_DN, GOBP_MICROTUBULE_BASED_TRANSPORT, GLI3_TARGET_GENES, ZFHX3_TARGET_GENES

GO Biological Process (1): intraciliary transport (GO:0042073)

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

GO Cellular Component (1): axoneme (GO:0005930)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cilium	1
transport along microtubule	1
cilium organization	1
binding	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

835 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCA5L	PSMG1	O95456	698
LCA5L	SH3BGR	P55822	651
LCA5L	KRTAP21-2	Q3LI59	585
LCA5L	SH3BGRL	O75368	568
LCA5L	MTMR9	Q96QG7	542
LCA5L	XKR6	Q5GH73	539
LCA5L	FAM178B	Q8IXR5	531
LCA5L	B3GALT5	Q9Y2C3	529
LCA5L	PFDN5	Q99471	497
LCA5L	CCM2	Q9BSQ5	488
LCA5L	LCA5	Q86VQ0	472
LCA5L	BRWD1	Q9NSI6	464
LCA5L	CCDC60	Q8IWA6	457
LCA5L	STON1	Q9Y6Q2	431
LCA5L	RSPH1	Q8WYR4	402

IntAct

104 interactions, top by confidence:

A	B	Type	Score
TPM3	LCA5L	psi-mi:“MI:0915”(physical association)	0.670
LCA5L	TFIP11	psi-mi:“MI:0915”(physical association)	0.670
LCA5L	TPM3	psi-mi:“MI:0915”(physical association)	0.670
TFIP11	LCA5L	psi-mi:“MI:0915”(physical association)	0.670
LCA5L	NMI	psi-mi:“MI:0915”(physical association)	0.560
TPM3	LCA5L	psi-mi:“MI:0915”(physical association)	0.560
NMI	LCA5L	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	TPM3	psi-mi:“MI:0915”(physical association)	0.560
	LCA5L	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	PRPH	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	EXOSC5	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	PBXIP1	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	KRT75	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	KRT76	psi-mi:“MI:0915”(physical association)	0.560
FCHSD2	LCA5L	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	CCDC197	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	KRT80	psi-mi:“MI:0915”(physical association)	0.560
LCA5L	TSGA10IP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (37): LCA5L (Two-hybrid), LCA5L (Two-hybrid), LCA5L (Two-hybrid), LCA5L (Two-hybrid), LCA5L (Affinity Capture-MS), PCM1 (Affinity Capture-MS), LCA5L (Affinity Capture-MS), LCA5L (Two-hybrid), LCA5L (Two-hybrid), LCA5L (Two-hybrid), LCA5L (Two-hybrid), PBXIP1 (Two-hybrid), IKBIP (Two-hybrid), KRT80 (Two-hybrid), KRT75 (Two-hybrid)

ESM2 similar proteins: A0AUZ9, A0JMF7, A1L2Y1, A3KMW7, A8MT70, A8MW92, A9JRX0, B0CM36, B0S6S9, B7ZS37, D3Z987, F1QB81, O95447, P40649, Q0IHW6, Q0P5X5, Q14B48, Q15468, Q3U285, Q3V089, Q49A88, Q4R815, Q4V9H5, Q5CZC0, Q5DTI6, Q5REF4, Q5T1N1, Q5ZJK5, Q66H35, Q6NRH7, Q6NRK3, Q6ZRS4, Q6ZU52, Q80VP2, Q80WQ8, Q8BLG0, Q8CB14, Q8CCJ9, Q8IUR6, Q8IX21

Diamond homologs: A7E3D8, B0CM36, O95447, Q4R3Q7, Q5U2Y9, Q80ST9, Q86VQ0, Q8C0X0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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.

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	5	48.1×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1015 predictions. Top by Δscore:

Variant	Effect	Δscore
21:39406611:ATC:A	acceptor_loss	1.0000
21:39406612:TC:T	acceptor_loss	1.0000
21:39406613:C:A	acceptor_loss	1.0000
21:39406613:C:CC	acceptor_gain	1.0000
21:39409974:ATTAC:A	donor_loss	1.0000
21:39409975:TTAC:T	donor_loss	1.0000
21:39409976:TACCT:T	donor_loss	1.0000
21:39409977:A:AC	donor_gain	1.0000
21:39409978:C:CC	donor_gain	1.0000
21:39409978:C:CG	donor_loss	1.0000
21:39409978:CCTT:C	donor_gain	1.0000
21:39409995:AGAAT:A	donor_gain	1.0000
21:39410094:ACCCT:A	acceptor_loss	1.0000
21:39410097:C:CC	acceptor_gain	1.0000
21:39410099:G:GC	acceptor_gain	1.0000
21:39410104:T:C	acceptor_gain	1.0000
21:39410104:T:TC	acceptor_gain	1.0000
21:39420734:T:TA	donor_gain	1.0000
21:39420842:CT:C	acceptor_gain	1.0000
21:39406608:TAAAT:T	acceptor_gain	0.9900
21:39410092:TTACC:T	acceptor_gain	0.9900
21:39410093:TACC:T	acceptor_gain	0.9900
21:39410094:ACC:A	acceptor_gain	0.9900
21:39410095:CC:C	acceptor_gain	0.9900
21:39410095:CCC:C	acceptor_gain	0.9900
21:39410096:CC:C	acceptor_gain	0.9900
21:39410099:G:C	acceptor_gain	0.9900
21:39410102:A:AC	acceptor_gain	0.9900
21:39410102:A:C	acceptor_gain	0.9900
21:39410103:T:TC	acceptor_gain	0.9900

AlphaMissense

4455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:39423034:A:G	L260P	0.987
21:39423172:A:G	L214P	0.986
21:39423260:C:G	A185P	0.986
21:39406317:G:C	F526L	0.985
21:39406317:G:T	F526L	0.985
21:39406319:A:G	F526L	0.985
21:39423130:A:G	L228P	0.985
21:39406086:A:C	F603L	0.984
21:39406086:A:T	F603L	0.984
21:39406088:A:G	F603L	0.984
21:39423280:A:G	L178P	0.984
21:39420722:A:G	L320P	0.983
21:39420710:A:G	L324P	0.981
21:39423079:A:G	L245P	0.981
21:39423164:A:G	S217P	0.981
21:39411792:C:G	R329P	0.980
21:39411786:A:G	L331P	0.978
21:39420827:A:G	L285P	0.978
21:39420765:C:G	A306P	0.977
21:39406297:A:G	L533P	0.976
21:39423175:A:G	L213P	0.975
21:39406090:A:G	L602P	0.974
21:39423205:T:G	H203P	0.974
21:39423352:A:G	L154P	0.971
21:39411759:C:G	R340P	0.970
21:39423052:A:G	L254P	0.968
21:39420794:A:G	L296P	0.963
21:39420800:C:G	R294P	0.963
21:39423042:C:A	R257S	0.962
21:39423042:C:G	R257S	0.962

dbSNP variants (sampled 300 via entrez): RS1000007702 (21:39431803 A>G), RS1000123303 (21:39431503 AAT>A), RS1000134360 (21:39445607 T>G), RS1000186755 (21:39406547 C>G,T), RS1000377015 (21:39409685 T>G), RS1000438592 (21:39418699 C>T), RS1000441317 (21:39439980 T>C), RS1000516915 (21:39416451 G>A), RS1000563144 (21:39408495 T>C), RS1000611342 (21:39421368 G>A,T), RS1000622679 (21:39421178 C>T), RS1000721147 (21:39414734 CTCTCTCTCTG>C), RS1000786001 (21:39413496 G>A), RS1000819447 (21:39427555 A>G), RS1000875928 (21:39434671 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004068_64	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	9.000000e-06
GCST006629_25	Pulse pressure	1.000000e-09
GCST010204_176	Low density lipoprotein cholesterol levels	1.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	3
Air Pollutants	increases abundance, increases expression	2
bisphenol A	increases methylation, affects cotreatment	1
1,6-hexamethylene diisocyanate	increases methylation	1
sodium arsenite	increases expression	1
bisphenol S	increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Smoke	increases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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