C1orf146

Summary

C1orf146 (chromosome 1 open reading frame 146, HGNC:24032) is a protein-coding gene on chromosome 1p22.1, encoding Protein SPO16 homolog (Q5VVC0). Plays a key role in reinforcing the integrity of the central element of the synaptonemal complex (SC) thereby stabilizing SC, ensuring progression of meiotic prophase I in male and female germ cells.

Predicted to be involved in reciprocal meiotic recombination and synaptonemal complex assembly. Predicted to be active in chromosome.

Source: NCBI Gene 388649 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 8 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001012425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24032
Approved symbol	C1orf146
Name	chromosome 1 open reading frame 146
Location	1p22.1
Locus type	gene with protein product
Status	Approved
Aliases	SPO16, SCRE
Ensembl gene	ENSG00000203910
Ensembl biotype	protein_coding
OMIM	618968
Entrez	388649

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000370373, ENST00000370375

RefSeq mRNA: 1 — MANE Select: NM_001012425 NM_001012425

CCDS: CCDS30772

Canonical transcript exons

ENST00000370375 — 6 exons

Exon	Start	End
ENSE00001452525	92245540	92245813
ENSE00001452527	92244779	92244857
ENSE00001452533	92217915	92218048
ENSE00003489923	92244217	92244385
ENSE00003667341	92231382	92231486
ENSE00003689536	92242212	92242305

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 88.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0086 / max 5.8641, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4036	0.0086	6

Top tissues by expression

129 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	88.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.87	gold quality
testis	UBERON:0000473	70.18	gold quality
right testis	UBERON:0004534	70.18	gold quality
left testis	UBERON:0004533	69.25	gold quality
cerebellar hemisphere	UBERON:0002245	65.76	gold quality
cerebellar cortex	UBERON:0002129	65.60	gold quality
cerebellum	UBERON:0002037	65.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	64.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	60.29	gold quality
primary visual cortex	UBERON:0002436	58.22	gold quality
right frontal lobe	UBERON:0002810	57.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.19	gold quality
superior frontal gyrus	UBERON:0002661	56.43	gold quality
anterior cingulate cortex	UBERON:0009835	53.43	gold quality
nucleus accumbens	UBERON:0001882	52.03	gold quality
cerebral cortex	UBERON:0000956	51.76	gold quality
granulocyte	CL:0000094	51.26	silver quality
brain	UBERON:0000955	50.70	gold quality
frontal cortex	UBERON:0001870	50.08	gold quality
caudate nucleus	UBERON:0001873	49.72	gold quality
right lung	UBERON:0002167	49.57	gold quality
mucosa of stomach	UBERON:0001199	49.07	gold quality
putamen	UBERON:0001874	49.00	gold quality
smooth muscle tissue	UBERON:0001135	48.28	gold quality
right ovary	UBERON:0002118	47.95	gold quality
vermiform appendix	UBERON:0001154	46.52	gold quality
skin of abdomen	UBERON:0001416	46.41	gold quality
Ammon’s horn	UBERON:0001954	46.07	gold quality
endometrium	UBERON:0001295	46.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting C1orf146, 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-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-6830-3P	98.62	68.07	1760

Literature-anchored findings (GeneRIF, showing 1)

• Pathogenic bi-allelic variants of meiotic ZMM complex gene SPO16 in premature ovarian insufficiency. (PMID:37270785)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	1700028K03Rik	ENSMUSG00000089798
rattus_norvegicus		ENSRNOG00000074494

Protein

Protein identifiers

Protein SPO16 homolog — Q5VVC0 (reviewed: Q5VVC0)

Alternative names: Synaptonemal complex reinforcing element

All UniProt accessions (2): Q5VVC0, X6R7K4

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in reinforcing the integrity of the central element of the synaptonemal complex (SC) thereby stabilizing SC, ensuring progression of meiotic prophase I in male and female germ cells. Promotes homologous recombination and crossing-over in meiotic prophase I via its association with SHOC1. Required for the localization of TEX11 and MSH4 to recombination intermediates.

Subunit / interactions. Homooligomer. Interacts with SHOC, SYCP1 and SYCE3.

Subcellular location. Chromosome.

RefSeq proteins (1): NP_001012425* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027857	SCRE	Family

Pfam: PF15162

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VVC0-F1	86.23	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 25 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_SYNAPTONEMAL_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, chr1p22, GOBP_HOMOLOGOUS_CHROMOSOME_PAIRING_AT_MEIOSIS, GOBP_NUCLEAR_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE, GOBP_CELL_CYCLE_PROCESS, GOBP_DNA_METABOLIC_PROCESS, GOBP_DNA_RECOMBINATION, GOBP_CHROMOSOME_SEGREGATION

GO Biological Process (3): synaptonemal complex assembly (GO:0007130), reciprocal meiotic recombination (GO:0007131), meiotic cell cycle (GO:0051321)

GO Molecular Function (0):

GO Cellular Component (1): chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
homologous chromosome pairing at meiosis	1
cellular component assembly	1
chromosome organization involved in meiotic cell cycle	1
synaptonemal complex organization	1
meiosis I	1
reciprocal homologous recombination	1
meiotic cell cycle process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1orf146	HFM1	A2PYH4	885
C1orf146	MSH4	O15457	861
C1orf146	SLC39A1	Q9NY26	821
C1orf146	MSH5	O43196	808
C1orf146	TEX11	Q8IYF3	798
C1orf146	SLC39A14	Q15043	690
C1orf146	SHOC1	Q5VXU9	666
C1orf146	EME1	Q96AY2	610
C1orf146	SPO11	Q9Y5K1	609
C1orf146	RNF212	Q495C1	608
C1orf146	MUS81	Q96NY9	528
C1orf146	CCNB1IP1	Q9NPC3	521
C1orf146	CDIN1	Q9Y2V0	509
C1orf146	SHOC2	Q9UQ13	473
C1orf146	SYCP1	Q15431	441

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SPO16	CST8	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): CST8 (Affinity Capture-MS), LMO1 (Affinity Capture-MS), CDSN (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), SBSN (Affinity Capture-MS), TSC22D4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1P8AUY4, A7RP64, B0R160, B4IB36, B4QL99, C5DLJ0, C5H8J1, F4IDW9, F4JIN3, O14251, O43114, O94536, P06838, P34281, P87231, Q04149, Q09693, Q12129, Q17423, Q19272, Q1EHT7, Q22006, Q29FC1, Q29IG6, Q2TA05, Q3KQP7, Q55FE3, Q59NG5, Q5VVC0, Q6BJ48, Q6C5F1, Q6CPQ8, Q6DDB9, Q6FYA6, Q6L5B5, Q6NSW5, Q6VBQ6, Q6VEU3, Q752A3, Q754C9

Diamond homologs: Q2TA05, Q3KQP7, Q5VVC0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1527159	GRCh37/hg19 1p22.1(chr1:92626657-93345442)	Pathogenic
3061757	NM_001012425.2(C1orf146):c.266del (p.Leu89fs)	Likely pathogenic

SpliceAI

926 predictions. Top by Δscore:

Variant	Effect	Δscore
1:92218004:G:GT	donor_gain	1.0000
1:92242206:A:G	acceptor_gain	1.0000
1:92244216:GGA:G	acceptor_gain	1.0000
1:92218044:AGCAG:A	donor_loss	0.9900
1:92218046:CAGG:C	donor_loss	0.9900
1:92218047:AG:A	donor_loss	0.9900
1:92218048:GGTG:G	donor_loss	0.9900
1:92218049:G:C	donor_loss	0.9900
1:92218050:T:G	donor_loss	0.9900
1:92218398:A:T	donor_gain	0.9900
1:92242194:T:A	acceptor_gain	0.9900
1:92242205:A:AG	acceptor_gain	0.9900
1:92244381:CAGAG:C	donor_loss	0.9900
1:92244382:AGAGG:A	donor_loss	0.9900
1:92244383:GAG:G	donor_gain	0.9900
1:92244384:AGG:A	donor_loss	0.9900
1:92244385:GG:G	donor_loss	0.9900
1:92244386:GT:G	donor_loss	0.9900
1:92244387:T:A	donor_loss	0.9900
1:92218045:GCAG:G	donor_gain	0.9800
1:92218397:G:T	donor_gain	0.9800
1:92244211:TCCTA:T	acceptor_loss	0.9800
1:92244212:CCTAG:C	acceptor_loss	0.9800
1:92244214:TAG:T	acceptor_loss	0.9800
1:92244215:A:AC	acceptor_loss	0.9800
1:92245538:A:AG	acceptor_gain	0.9800
1:92245539:G:GG	acceptor_gain	0.9800
1:92223164:T:A	acceptor_gain	0.9700
1:92244215:A:AG	acceptor_gain	0.9700
1:92244216:G:GG	acceptor_gain	0.9700

AlphaMissense

1184 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:92245612:A:C	S161R	0.980
1:92245614:T:A	S161R	0.980
1:92245614:T:G	S161R	0.980
1:92231472:A:C	S18R	0.976
1:92231474:C:A	S18R	0.976
1:92231474:C:G	S18R	0.976
1:92244225:T:C	F57L	0.974
1:92244227:T:A	F57L	0.974
1:92244227:T:G	F57L	0.974
1:92244325:T:A	V90D	0.968
1:92244223:C:A	A56E	0.965
1:92244226:T:C	F57S	0.964
1:92242258:G:C	R38P	0.962
1:92244294:T:C	F80L	0.955
1:92244296:T:A	F80L	0.955
1:92244296:T:G	F80L	0.955
1:92244780:T:C	F111L	0.955
1:92244782:C:A	F111L	0.955
1:92244782:C:G	F111L	0.955
1:92244802:T:A	I118K	0.955
1:92231451:T:A	W11R	0.952
1:92231451:T:C	W11R	0.952
1:92244318:T:C	F88L	0.949
1:92244320:T:A	F88L	0.949
1:92244320:T:G	F88L	0.949
1:92244802:T:G	I118R	0.938
1:92244805:T:C	L119P	0.937
1:92244306:C:G	H84D	0.936
1:92244295:T:C	F80S	0.931
1:92244852:G:C	A135P	0.929

dbSNP variants (sampled 300 via entrez): RS1000179844 (1:92232227 T>G), RS1000300100 (1:92243331 G>A,C), RS1000332056 (1:92243554 T>C), RS1000344774 (1:92222130 A>G), RS1000494490 (1:92227313 C>A,T), RS1000560847 (1:92243232 C>G), RS1000635516 (1:92227708 T>C), RS1000786602 (1:92233278 A>T), RS1000863546 (1:92237969 G>A), RS1001148177 (1:92227432 A>G), RS1001164124 (1:92244611 T>G), RS1001213426 (1:92237615 C>T), RS1001215619 (1:92233089 A>G), RS1001258278 (1:92244867 C>G), RS1001269892 (1:92227151 A>G)

Disease associations

OMIM: gene MIM:618968 | disease phenotypes: MIM:613107

GenCC curated gene-disease

Mondo (2): male infertility (MONDO:0005372), neutropenia, severe congenital, 2, autosomal dominant (MONDO:0013139)

Orphanet (1): Autosomal dominant severe congenital neutropenia (Orphanet:486)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003622_22	Systemic lupus erythematosus	6.000000e-07

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
C567748	Neutropenia, Severe Congenital, Autosomal Dominant 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia