SOFU1

Summary

SOFU1 (sperm-oocyte fusion factor 1, HGNC:21750) is a protein-coding gene on chromosome 7q34, encoding Sperm-egg fusion protein LLCFC1 (Q96L11). Sperm protein required for fusion of sperm with the egg membrane during fertilization.

Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization. Predicted to be located in extracellular region.

Source: NCBI Gene 135927 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001382496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21750
Approved symbol	SOFU1
Name	sperm-oocyte fusion factor 1
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	CTM-1, SOF1
Ensembl gene	ENSG00000165131
Ensembl biotype	protein_coding
OMIM	618946
Entrez	135927

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000409607, ENST00000458732

RefSeq mRNA: 1 — MANE Select: NM_001382496 NM_001382496

CCDS: CCDS5876

Canonical transcript exons

ENST00000409607 — 2 exons

Exon	Start	End
ENSE00001584889	142939484	142939754
ENSE00001589670	142940352	142940868

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 97.26.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0181 / max 14.8858, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81744	0.0149	3
81743	0.0032	2

Top tissues by expression

119 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	97.26	gold quality
left testis	UBERON:0004533	94.60	gold quality
right testis	UBERON:0004534	94.17	gold quality
testis	UBERON:0000473	93.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	70.71	gold quality
blood	UBERON:0000178	70.63	gold quality
corpus callosum	UBERON:0002336	66.69	gold quality
substantia nigra	UBERON:0002038	58.36	gold quality
spleen	UBERON:0002106	58.25	gold quality
bone marrow	UBERON:0002371	57.37	gold quality
primary visual cortex	UBERON:0002436	55.95	gold quality
Ammon’s horn	UBERON:0001954	53.38	gold quality
endocervix	UBERON:0000458	53.14	gold quality
tonsil	UBERON:0002372	53.00	gold quality
lymph node	UBERON:0000029	51.41	gold quality
putamen	UBERON:0001874	51.29	gold quality
monocyte	CL:0000576	50.92	silver quality
leukocyte	CL:0000738	49.59	silver quality
ganglionic eminence	UBERON:0004023	49.09	gold quality
skeletal muscle tissue	UBERON:0001134	48.64	gold quality
hypothalamus	UBERON:0001898	48.59	gold quality
amygdala	UBERON:0001876	48.48	gold quality
right coronary artery	UBERON:0001625	48.21	gold quality
temporal lobe	UBERON:0001871	48.21	gold quality
apex of heart	UBERON:0002098	48.04	gold quality
muscle tissue	UBERON:0002385	48.02	gold quality
bone marrow cell	CL:0002092	47.80	gold quality
caudate nucleus	UBERON:0001873	47.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.43	gold quality
descending thoracic aorta	UBERON:0002345	46.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting SOFU1, 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-10401-5P	99.99	65.79	948
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-1291	96.28	65.89	1224

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Llcfc1	ENSMUSG00000029867
rattus_norvegicus	Llcfc1	ENSRNOG00000025618

Protein

Protein identifiers

Sperm-egg fusion protein LLCFC1 — Q96L11 (reviewed: Q96L11)

Alternative names: LLLL and CFNLAS motif-containing protein 1, MSSP-binding protein CTM-1, Sperm-oocyte fusion required protein 1

All UniProt accessions (2): A0A2Y9D021, Q96L11

UniProt curated annotations — full annotation on UniProt →

Function. Sperm protein required for fusion of sperm with the egg membrane during fertilization.

Subcellular location. Secreted.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96L11-1	1, CTM-1beta	yes
Q96L11-2	2, CTM-1alpha
Q96L11-3	3

RefSeq proteins (1): NP_001369425* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031684	LLCFC1	Family

Pfam: PF15838

UniProt features (7 total): splice variant 3, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96L11-F1	60.93	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 41 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, TGACATY_UNKNOWN, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, VDR_Q3, GOBP_PLASMA_MEMBRANE_FUSION, GOBP_MEMBRANE_ORGANIZATION, GOBP_FERTILIZATION, TGGAAA_NFAT_Q4_01, BRUINS_UVC_RESPONSE_EARLY_LATE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR1290, MIR8085

GO Biological Process (2): fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), single fertilization (GO:0007338)

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
single fertilization	1
cellular process involved in reproduction in multicellular organism	1
fertilization	1
cellular anatomical structure	1

Protein interactions and networks

STRING

136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOFU1	TMEM95	Q3KNT9	631
SOFU1	SPACA6	W5XKT8	541
SOFU1	SETBP1	Q9Y6X0	512
SOFU1	IZUMO1	Q8IYV9	465
SOFU1	NBEAL1	Q6ZS30	401
SOFU1	SAXO6	Q8TC05	350
SOFU1	HEMK1	Q9Y5R4	348
SOFU1	EPB41L1	Q9H4G0	324
SOFU1	MTURN	Q8N3F0	308
SOFU1	NTS	P30990	292
SOFU1	EEF1AKMT4	P0DPD7	290
SOFU1	TYW2	Q53H54	288
SOFU1	CYREN	Q9BWK5	288
SOFU1	EMC10	Q5UCC4	256
SOFU1	FLOT2	Q14254	256

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CFTR	LLCFC1	psi-mi:“MI:0915”(physical association)	0.370
ZBTB48	LLCFC1	psi-mi:“MI:0915”(physical association)	0.370
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): C7orf34 (Two-hybrid), MAN2A1 (Affinity Capture-MS), MAN2B1 (Affinity Capture-MS), MAN2A2 (Affinity Capture-MS), WNT5A (Affinity Capture-MS), DHFRL1 (Affinity Capture-MS), TMEM131 (Affinity Capture-MS), TOR1B (Affinity Capture-MS), LAMA3 (Affinity Capture-MS), PXDN (Affinity Capture-MS), CNTNAP1 (Affinity Capture-MS), MELK (Affinity Capture-MS), SEMA3C (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), EOGT (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1N3, A0A1B0GTK4, A0A1B0GTR0, A0JNL8, A2RUT3, A4IFR0, C9JUS6, D3ZKM3, E9PXB6, F2Z3F1, O70899, O71302, O93195, O95411, P03165, P04610, P0C7M3, P12912, P13206, P20976, P20977, P29560, P47939, P47940, P69714, Q02919, Q08648, Q1RN00, Q1WG82, Q5PR19, Q66669, Q67923, Q69027, Q69604, Q6PDA7, Q6UWK7, Q80IU5, Q80IU8, Q8N5N4, Q913A9

Diamond homologs: Q96L11, Q9D9P8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

228 predictions. Top by Δscore:

Variant	Effect	Δscore
7:142940344:T:TA	acceptor_gain	0.9900
7:142940350:A:AG	acceptor_gain	0.9900
7:142940351:G:GG	acceptor_gain	0.9900
7:142940351:GACC:G	acceptor_gain	0.9900
7:142940351:GACCA:G	acceptor_gain	0.9900
7:142940349:CAGAC:C	acceptor_loss	0.9800
7:142940350:A:AC	acceptor_loss	0.9800
7:142940351:G:GT	acceptor_loss	0.9800
7:142940351:GA:G	acceptor_gain	0.9700
7:142940351:GAC:G	acceptor_gain	0.9700
7:142939527:GGT:G	donor_gain	0.9600
7:142939750:TGCAG:T	donor_loss	0.9600
7:142939752:CAG:C	donor_loss	0.9600
7:142939754:GG:G	donor_loss	0.9600
7:142939759:G:C	donor_loss	0.9100
7:142939556:G:GT	donor_gain	0.9000
7:142939757:A:C	donor_loss	0.8900
7:142939758:GG:G	donor_loss	0.8400
7:142939528:GT:G	donor_gain	0.8300
7:142939529:TT:T	donor_gain	0.8300
7:142939529:T:G	donor_gain	0.8000
7:142939583:G:GT	donor_gain	0.7800
7:142940307:AGGC:A	acceptor_gain	0.7800
7:142939689:TG:T	donor_gain	0.6900
7:142939755:G:GG	donor_gain	0.6800
7:142940320:GGCTC:G	acceptor_gain	0.6600
7:142940349:C:G	acceptor_gain	0.6500
7:142940350:A:G	acceptor_gain	0.6500
7:142940303:G:T	acceptor_gain	0.6300
7:142940305:TCAGG:T	acceptor_gain	0.6300

AlphaMissense

968 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000200856 (7:142938033 C>T), RS1000484211 (7:142939119 T>C), RS1002936225 (7:142940894 T>A), RS1004598054 (7:142940007 T>G), RS1004665132 (7:142938763 C>A,G,T), RS1005300745 (7:142939132 A>G), RS1006362457 (7:142940319 G>C), RS1007454734 (7:142940738 G>A,C), RS1009748176 (7:142938089 G>C,T), RS1009772252 (7:142938452 C>T), RS1010453097 (7:142941114 T>C), RS1012195980 (7:142940209 G>T), RS1013812845 (7:142938418 C>G), RS1014681130 (7:142940342 C>A,T), RS1015041158 (7:142940518 G>A,C,T)

Disease associations

OMIM: gene MIM:618946 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004860_10	Alcoholic chronic pancreatitis	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	increases expression	1
2-palmitoylglycerol	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Folic Acid	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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