C16orf96

Summary

C16orf96 (chromosome 16 open reading frame 96, HGNC:40031) is a protein-coding gene on chromosome 16p13.3, encoding Uncharacterized protein C16orf96 (A6NNT2).

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 40 total — 1 pathogenic
• MANE Select transcript: NM_001145011

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40031
Approved symbol	C16orf96
Name	chromosome 16 open reading frame 96
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205832
Ensembl biotype	protein_coding
Entrez	342346

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000444310

RefSeq mRNA: 2 — MANE Select: NM_001145011 NM_001145011, NM_001387219

CCDS: CCDS53986

Canonical transcript exons

ENST00000444310 — 16 exons

Exon	Start	End
ENSE00001490629	4574972	4575058
ENSE00001490631	4574709	4574789
ENSE00001490633	4571561	4571665
ENSE00001490634	4556340	4556909
ENSE00001561716	4575174	4576635
ENSE00001613881	4599284	4599364
ENSE00001633174	4580015	4580125
ENSE00001649909	4594704	4594803
ENSE00001653952	4587039	4587113
ENSE00001685113	4578940	4579025
ENSE00001687898	4600100	4600758
ENSE00001694446	4594351	4594510
ENSE00001714740	4591666	4591784
ENSE00001715676	4593224	4593316
ENSE00001740838	4588167	4588331
ENSE00001803286	4592305	4592367

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 75.07.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0400 / max 45.1085, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152474	0.0241	4
152473	0.0159	3

Top tissues by expression

95 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	75.07	silver quality
left testis	UBERON:0004533	74.65	gold quality
testis	UBERON:0000473	74.35	gold quality
right testis	UBERON:0004534	73.96	gold quality
cortical plate	UBERON:0005343	53.88	gold quality
prefrontal cortex	UBERON:0000451	52.81	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	52.76	gold quality
bone marrow cell	CL:0002092	52.31	gold quality
substantia nigra	UBERON:0002038	52.04	gold quality
ventricular zone	UBERON:0003053	51.99	silver quality
granulocyte	CL:0000094	51.30	silver quality
frontal cortex	UBERON:0001870	50.96	gold quality
putamen	UBERON:0001874	50.82	gold quality
nucleus accumbens	UBERON:0001882	50.15	gold quality
caudate nucleus	UBERON:0001873	50.01	gold quality
liver	UBERON:0002107	49.87	silver quality
hindlimb stylopod muscle	UBERON:0004252	49.71	silver quality
bone marrow	UBERON:0002371	49.43	gold quality
temporal lobe	UBERON:0001871	49.42	gold quality
amygdala	UBERON:0001876	49.31	gold quality
cerebral cortex	UBERON:0000956	49.07	gold quality
ganglionic eminence	UBERON:0004023	48.80	gold quality
right lobe of liver	UBERON:0001114	48.63	silver quality
primary visual cortex	UBERON:0002436	48.56	silver quality
right frontal lobe	UBERON:0002810	48.55	gold quality
Ammon’s horn	UBERON:0001954	48.37	gold quality
body of pancreas	UBERON:0001150	48.22	silver quality
hypothalamus	UBERON:0001898	48.14	gold quality
brain	UBERON:0000955	48.05	gold quality
pancreas	UBERON:0001264	48.05	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.61

Regulation

Is transcription factor: no

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	zp2l2	ENSDARG00000004898
danio_rerio	zp2l1	ENSDARG00000055415
danio_rerio	zpax4	ENSDARG00000079034
danio_rerio	zp2.1	ENSDARG00000086352
danio_rerio	zp2.5	ENSDARG00000086522
danio_rerio	si:zfos-1505d6.3	ENSDARG00000089966
danio_rerio	zp2.3	ENSDARG00000090237
danio_rerio	zp2.6	ENSDARG00000091409
danio_rerio	zp2.2	ENSDARG00000105346
mus_musculus	4930562C15Rik	ENSMUSG00000022518
rattus_norvegicus		ENSRNOG00000084991

Paralogs (4): ZP2 (ENSG00000103310), ZP4 (ENSG00000116996), QRICH2 (ENSG00000129646), ZP1 (ENSG00000149506)

Protein

Protein identifiers

Uncharacterized protein C16orf96 — A6NNT2 (reviewed: A6NNT2)

All UniProt accessions (1): A6NNT2

RefSeq proteins (2): NP_001138483, NP_001374148 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032013	DUF4795	Domain

Pfam: PF16043

UniProt features (11 total): region of interest 4, compositionally biased region 3, coiled-coil region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NNT2-F1	56.19	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (showing top): DARWICHE_PAPILLOMA_PROGRESSION_RISK, ZNF664_TARGET_GENES, GSE14026_TH1_VS_TH17_UP, GSE20366_TREG_VS_NAIVE_CD4_TCELL_DN, GSE19888_ADENOSINE_A3R_INH_VS_ACT_WITH_INHIBITOR_PRETREATMENT_IN_MAST_CELL_DN, GSE24972_MARGINAL_ZONE_BCELL_VS_FOLLICULAR_BCELL_DN, GSE32533_MIR17_KO_VS_MIR17_OVEREXPRESS_ACT_CD4_TCELL_UP, GSE26351_UNSTIM_VS_BMP_PATHWAY_STIM_HEMATOPOIETIC_PROGENITORS_DN, chr16p13, GSE40274_FOXP3_VS_FOXP3_AND_GATA1_TRANSDUCED_ACTIVATED_CD4_TCELL_UP, GSE43863_TH1_VS_TFH_EFFECTOR_CD4_TCELL_UP, GSE41176_UNSTIM_VS_ANTI_IGM_STIM_BCELL_24H_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

843 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C16orf96	ZNF142	P52746	610
C16orf96	FAM194C	Q8ND61	570
C16orf96	SLC38A11	Q08AI6	551
C16orf96	GLB1L	Q6UWU2	510
C16orf96	EBLN1	P0CF75	505
C16orf96	UBALD1	Q8TB05	447
C16orf96	ZFP69B	Q9UJL9	433
C16orf96	MYCBPAP	Q8TBZ2	401
C16orf96	GPR45	Q9Y5Y3	397
C16orf96	BEAN1	Q3B7T3	380
C16orf96	TTC21B	Q7Z4L5	371
C16orf96	NMRAL1	Q9HBL8	352
C16orf96	WDR46	O15213	349
C16orf96	ARHGAP39	Q9C0H5	325
C16orf96	CCDC39	Q9UFE4	323

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530

BioGRID (9): C16orf96 (Affinity Capture-MS), C16orf96 (Affinity Capture-MS), C16orf96 (Affinity Capture-MS), C16orf96 (Affinity Capture-MS), C16orf96 (Affinity Capture-MS), C16orf96 (Proximity Label-MS), C16orf96 (Negative Genetic), C16orf96 (Proximity Label-MS), THRAP3 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1A5Q6, A6NF34, A6NNT2, B0BF33, D3ZF92, O43278, O75509, O88393, P08920, P08921, P25236, P26342, P35054, P49907, P49908, P51843, P70274, P70503, P79386, Q03167, Q05469, Q13342, Q1LVK9, Q4JF29, Q4R7B7, Q5F378, Q5QGU6, Q5R8W9, Q61066, Q6AY06, Q6P7C7, Q6S545, Q8BHP7, Q8BVM2, Q8VHF2, Q91ZV2, Q921T2, Q96PD2, Q99P91, Q99PS8

Diamond homologs: A6NNT2, E9QMW4, Q3V2A7, Q9H0J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	21
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685643	GRCh37/hg19 16p13.3(chr16:3731117-5325699)x3	Pathogenic

SpliceAI

2268 predictions. Top by Δscore:

Variant	Effect	Δscore
16:4556906:CAAGG:C	donor_loss	1.0000
16:4556907:AAGGT:A	donor_loss	1.0000
16:4556908:AGG:A	donor_loss	1.0000
16:4556909:GGTAC:G	donor_loss	1.0000
16:4556910:G:C	donor_loss	1.0000
16:4556911:T:A	donor_loss	1.0000
16:4571559:A:AG	acceptor_gain	1.0000
16:4571560:G:GT	acceptor_gain	1.0000
16:4571560:GT:G	acceptor_gain	1.0000
16:4571560:GTC:G	acceptor_gain	1.0000
16:4571560:GTCA:G	acceptor_gain	1.0000
16:4571560:GTCAA:G	acceptor_gain	1.0000
16:4571663:AAGGT:A	donor_loss	1.0000
16:4571664:AGGT:A	donor_loss	1.0000
16:4571666:G:C	donor_loss	1.0000
16:4571667:T:A	donor_loss	1.0000
16:4574704:GACAG:G	acceptor_loss	1.0000
16:4574707:A:AG	acceptor_gain	1.0000
16:4574707:AGGTA:A	acceptor_loss	1.0000
16:4574708:G:GG	acceptor_gain	1.0000
16:4574784:G:GT	donor_gain	1.0000
16:4574784:G:T	donor_gain	1.0000
16:4574786:AGTGG:A	donor_loss	1.0000
16:4574787:GTG:G	donor_gain	1.0000
16:4574788:TGG:T	donor_loss	1.0000
16:4574790:G:GA	donor_loss	1.0000
16:4574791:T:G	donor_loss	1.0000
16:4575054:CCTCA:C	donor_gain	1.0000
16:4575055:CTCA:C	donor_gain	1.0000
16:4575059:GTGA:G	donor_gain	1.0000

AlphaMissense

7440 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:4575026:T:A	W221R	0.978
16:4575026:T:C	W221R	0.978
16:4556518:T:C	L10P	0.976
16:4575028:G:C	W221C	0.975
16:4575028:G:T	W221C	0.975
16:4576600:T:C	L707P	0.975
16:4576612:T:C	L711P	0.975
16:4556530:C:A	A14D	0.973
16:4576528:T:A	V683D	0.968
16:4579006:T:C	L741P	0.968
16:4574979:T:C	L205P	0.966
16:4576524:G:C	A682P	0.966
16:4575050:T:C	F229L	0.965
16:4575052:C:A	F229L	0.965
16:4575052:C:G	F229L	0.965
16:4571595:T:C	L152P	0.964
16:4580100:T:C	L776P	0.963
16:4571586:T:C	L149P	0.962
16:4571604:T:C	L155P	0.958
16:4591777:T:C	F902L	0.957
16:4591779:T:A	F902L	0.957
16:4591779:T:G	F902L	0.957
16:4574776:T:C	L198P	0.954
16:4587106:T:C	L807P	0.953
16:4576192:C:A	A571D	0.950
16:4576536:T:C	S686P	0.950
16:4571625:T:C	L162P	0.947
16:4575036:T:C	L224P	0.947
16:4556578:T:C	L30P	0.946
16:4576579:T:C	L700P	0.946

dbSNP variants (sampled 300 via entrez): RS1000006921 (16:4571351 A>G), RS1000046113 (16:4537465 G>A), RS1000064970 (16:4549846 C>G), RS1000110160 (16:4542030 G>C), RS1000115649 (16:4576524 G>A,C,T), RS1000143909 (16:4590634 C>T), RS1000151492 (16:4576343 A>C), RS1000160457 (16:4571921 C>A), RS1000197255 (16:4556950 C>T), RS1000256150 (16:4596062 G>A,C,T), RS1000283760 (16:4551842 A>C,G), RS1000297333 (16:4548597 G>A), RS1000367467 (16:4566080 C>T), RS1000419468 (16:4546177 G>C,T), RS1000420566 (16:4551550 C>G)

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

7 associations (top):

Study	Trait	p-value
GCST001762_670	Obesity-related traits	7.000000e-07
GCST90002394_533	Monocyte percentage of white cells	1.000000e-09
GCST90002402_176	Platelet count	2.000000e-09
GCST90020024_739	A body shape index	2.000000e-10
GCST90020024_740	A body shape index	4.000000e-08
GCST90020029_562	Waist circumference adjusted for body mass index	8.000000e-09
GCST90020029_563	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005119	antioxidant measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0004309	platelet count
EFO:0007789	BMI-adjusted waist circumference

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
Benzo(a)pyrene	affects methylation, decreases methylation, increases mutagenesis	3
propionaldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
Sunitinib	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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