LHFPL1

Summary

LHFPL1 (LHFPL tetraspan subfamily member 1, HGNC:6587) is a protein-coding gene on chromosome Xq23, encoding LHFPL tetraspan subfamily member 1 protein (Q86WI0).

This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in one LHFP-like gene result in deafness in humans and mice, and a second LHFP-like gene is fused to a high-mobility group gene in a translocation-associated lipoma. Alternatively spliced transcript variants have been found, but their biological validity has not been determined.

Source: NCBI Gene 340596 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_178175

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6587
Approved symbol	LHFPL1
Name	LHFPL tetraspan subfamily member 1
Location	Xq23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182508
Ensembl biotype	protein_coding
OMIM	300566
Entrez	340596

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371968, ENST00000478229, ENST00000864007, ENST00000864008, ENST00000864010, ENST00000922440, ENST00000922441, ENST00000922442, ENST00000922443

RefSeq mRNA: 1 — MANE Select: NM_178175 NM_178175

CCDS: CCDS14562

Canonical transcript exons

ENST00000371968 — 4 exons

Exon	Start	End
ENSE00001322535	112660627	112660725
ENSE00001456575	112630648	112631601
ENSE00001456578	112671009	112671404
ENSE00003844344	112679829	112679938

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 86.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2100 / max 26.5802, expressed in 81 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200199	0.2100	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.60	gold quality
nucleus accumbens	UBERON:0001882	65.94	gold quality
left coronary artery	UBERON:0001626	64.41	gold quality
right coronary artery	UBERON:0001625	64.29	gold quality
caudate nucleus	UBERON:0001873	63.13	gold quality
coronary artery	UBERON:0001621	63.09	gold quality
descending thoracic aorta	UBERON:0002345	60.10	gold quality
putamen	UBERON:0001874	59.68	gold quality
hypothalamus	UBERON:0001898	59.32	gold quality
substantia nigra	UBERON:0002038	59.07	gold quality
medial globus pallidus	UBERON:0002477	59.05	silver quality
pituitary gland	UBERON:0000007	58.57	gold quality
thoracic aorta	UBERON:0001515	58.13	gold quality
ascending aorta	UBERON:0001496	57.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	57.51	gold quality
amygdala	UBERON:0001876	57.24	gold quality
adenohypophysis	UBERON:0002196	57.23	gold quality
midbrain	UBERON:0001891	56.78	gold quality
anterior cingulate cortex	UBERON:0009835	55.98	gold quality
globus pallidus	UBERON:0001875	55.03	silver quality
forebrain	UBERON:0001890	53.65	gold quality
right lobe of thyroid gland	UBERON:0001119	53.26	gold quality
left lobe of thyroid gland	UBERON:0001120	52.86	gold quality
thyroid gland	UBERON:0002046	52.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.79	gold quality
brain	UBERON:0000955	51.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	51.11	gold quality
right frontal lobe	UBERON:0002810	50.68	gold quality
temporal lobe	UBERON:0001871	50.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting LHFPL1, 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-6835-3P	99.93	70.49	2904
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-12126	98.09	64.82	637
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-203B-3P	97.82	66.27	979
HSA-MIR-5089-3P	97.50	67.82	758

Literature-anchored findings (GeneRIF, showing 2)

• Expressed widely in ER of all tissues, especially highly in lung, thymus, skeleton muscle, colon and ovary. (PMID:15620218)
• The authors present an overview of the LHFP gene family in mouse and humans (PMID:15905332)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lhfpl1	ENSMUSG00000041700
rattus_norvegicus	Lhfpl1	ENSRNOG00000027601

Paralogs (6): LHFPL2 (ENSG00000145685), LHFPL4 (ENSG00000156959), LHFPL6 (ENSG00000183722), LHFPL3 (ENSG00000187416), LHFPL5 (ENSG00000197753), LHFPL7 (ENSG00000206069)

Protein

Protein identifiers

LHFPL tetraspan subfamily member 1 protein — Q86WI0 (reviewed: Q86WI0)

Alternative names: Lipoma HMGIC fusion partner-like 1 protein

All UniProt accessions (1): Q86WI0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Widely expressed. Expressed at high levels in lung, thymus, skeletal muscle, colon and ovary.

Similarity. Belongs to the LHFP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86WI0-1	1	yes
Q86WI0-2	2
Q86WI0-3	3

RefSeq proteins (1): NP_835469* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019372	LHFPL	Family

Pfam: PF10242

UniProt features (8 total): transmembrane region 3, splice variant 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WI0-F1	89.47	0.70

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): 153

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): PAX4_01, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, CAGCTG_AP4_Q5, PAX8_B, TGCTGAY_UNKNOWN, WTGAAAT_UNKNOWN, ARGGGTTAA_UNKNOWN, LYF1_01, NKX22_01, NKX25_01, RYTTCCTG_ETS2_B, GATA4_Q3, CART1_01, MEF2_Q6_01, PAX6_01

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LHFPL1	AMOT	Q4VCS5	617
LHFPL1	RTL4	Q6ZR62	613
LHFPL1	LRCH2	Q5VUJ6	580
LHFPL1	UBE4B	O95155	570
LHFPL1	LRRK1	Q38SD2	516
LHFPL1	ALG13	Q9NP73	487
LHFPL1	TRPC5	Q9UL62	456
LHFPL1	ANKRD40	Q6AI12	446
LHFPL1	HTR2C	P28335	415
LHFPL1	NXPE2	Q96DL1	400
LHFPL1	CTCF	P49711	394
LHFPL1	CEACAM20	Q6UY09	393
LHFPL1	RBP7	Q96R05	386
LHFPL1	ATRX	P46100	353
LHFPL1	TGM5	O43548	329

IntAct

18 interactions, top by confidence:

A	B	Type	Score
LAT	LHFPL1	psi-mi:“MI:0915”(physical association)	0.560
LHFPL1	THSD7A	psi-mi:“MI:0915”(physical association)	0.560
PLP2	LHFPL1	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	LHFPL1	psi-mi:“MI:0915”(physical association)	0.560
SEC22B	LHFPL1	psi-mi:“MI:0915”(physical association)	0.560
LHFPL1	TSPAN10	psi-mi:“MI:0915”(physical association)	0.400
LHFPL1	ADCY3	psi-mi:“MI:0914”(association)	0.350
THSD7A	LHFPL1	psi-mi:“MI:0915”(physical association)	0.000
PLP2	LHFPL1	psi-mi:“MI:0915”(physical association)	0.000
LAT	LHFPL1	psi-mi:“MI:0915”(physical association)	0.000
IGFBP5	LHFPL1	psi-mi:“MI:0915”(physical association)	0.000
SEC22B	LHFPL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): LHFPL1 (Two-hybrid), LHFPL1 (Two-hybrid), LHFPL1 (Two-hybrid), LAT (Two-hybrid), SEC22B (Two-hybrid), TSPAN10 (Affinity Capture-MS), TMEM259 (Affinity Capture-MS), RNF185 (Affinity Capture-MS), BSCL2 (Affinity Capture-MS), OSBPL5 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), SLC27A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NY17, A4IF75, B2RVY9, B3SHH9, F6V1J6, O42281, O70578, P19518, P97707, Q06432, Q08CE6, Q08DE1, Q0D289, Q0V9E0, Q14714, Q2MJQ7, Q4R4Z3, Q4V922, Q5CZV0, Q5PRC1, Q5RDV7, Q5XGU1, Q62147, Q66IV3, Q68FV0, Q6AZD1, Q6P0C6, Q6R5J2, Q6ZP80, Q6ZUX7, Q7ZZL8, Q86WI0, Q8BGA2, Q8NBL3, Q8VHW3, Q8VHW4, Q8VHW7, Q8VHW8, Q91Y55, Q925N4

Diamond homologs: Q5BJS2, Q5PRC1, Q6P0C6, Q80SV1, Q80WE5, Q86WI0, Q8BM86, Q9Y693, Q6DHB5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1059 predictions. Top by Δscore:

Variant	Effect	Δscore
X:112631598:GTACC:G	acceptor_loss	0.9800
X:112631599:TACCT:T	acceptor_loss	0.9800
X:112631601:CCTGT:C	acceptor_loss	0.9800
X:112631602:CT:C	acceptor_loss	0.9800
X:112631603:T:C	acceptor_loss	0.9800
X:112648638:CAAAG:C	donor_gain	0.9800
X:112653585:T:TA	donor_gain	0.9800
X:112631604:G:C	acceptor_loss	0.9700
X:112632984:C:A	donor_gain	0.9700
X:112632344:C:CT	donor_gain	0.9600
X:112671004:CTTA:C	donor_loss	0.9600
X:112671005:TTA:T	donor_loss	0.9600
X:112671006:TA:T	donor_loss	0.9600
X:112671007:A:AT	donor_loss	0.9600
X:112632941:T:TA	donor_gain	0.9400
X:112632339:CCCCG:C	donor_gain	0.9300
X:112632340:CCCGC:C	donor_gain	0.9300
X:112632341:CCGCC:C	donor_gain	0.9300
X:112632345:C:CT	donor_gain	0.9300
X:112653591:T:A	donor_gain	0.9300
X:112671405:C:CC	acceptor_gain	0.9300
X:112662415:ATTG:A	donor_gain	0.9200
X:112662418:G:A	donor_gain	0.9200
X:112632916:T:A	donor_gain	0.9100
X:112646161:T:TA	donor_gain	0.9000
X:112679824:TTTA:T	donor_loss	0.9000
X:112679825:TTACC:T	donor_loss	0.9000
X:112679826:TAC:T	donor_loss	0.9000
X:112679827:AC:A	donor_loss	0.9000
X:112679828:C:A	donor_loss	0.9000

AlphaMissense

1427 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:112660684:A:G	W142R	0.997
X:112660684:A:T	W142R	0.997
X:112671256:G:C	S45R	0.997
X:112671256:G:T	S45R	0.997
X:112671258:T:G	S45R	0.997
X:112660682:C:A	W142C	0.996
X:112660682:C:G	W142C	0.996
X:112660712:G:C	S132R	0.996
X:112660712:G:T	S132R	0.996
X:112660714:T:G	S132R	0.996
X:112671313:A:C	S26R	0.996
X:112671313:A:T	S26R	0.996
X:112671315:T:G	S26R	0.996
X:112660634:A:C	F158L	0.995
X:112660634:A:T	F158L	0.995
X:112660636:A:G	F158L	0.995
X:112671119:C:T	G91D	0.995
X:112671150:A:G	W81R	0.995
X:112671150:A:T	W81R	0.995
X:112671248:C:G	R48P	0.995
X:112671322:A:C	S23R	0.995
X:112671322:A:T	S23R	0.995
X:112671324:T:G	S23R	0.995
X:112660656:C:T	C151Y	0.994
X:112660696:A:C	Y138D	0.994
X:112671148:C:A	W81C	0.994
X:112671148:C:G	W81C	0.994
X:112671157:G:C	S78R	0.994
X:112671157:G:T	S78R	0.994
X:112671159:T:G	S78R	0.994

dbSNP variants (sampled 300 via entrez): RS1000011519 (X:112633350 C>A), RS1000031867 (X:112643391 A>G), RS1000050467 (X:112676590 C>T), RS1000103675 (X:112642813 T>A,C), RS1000120920 (X:112658695 A>C), RS1000281200 (X:112653559 C>T), RS1000304682 (X:112662189 T>C), RS1000309222 (X:112681149 T>G), RS1000376621 (X:112661813 C>G,T), RS1000479480 (X:112651683 T>C), RS1000502736 (X:112672192 T>C), RS1000535705 (X:112672793 C>A,G), RS1000634118 (X:112660478 C>T), RS1000648419 (X:112678826 G>C), RS1000791561 (X:112670004 T>A,C)

Disease associations

OMIM: gene MIM:300566 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases methylation, decreases expression	2
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
CGP 52608	affects binding, increases reaction	1
Diethylhexyl Phthalate	decreases expression	1
Silicon Dioxide	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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