Table 2 Twelve autosomal dominant positional candidate genes identified by in silico CNV mapping at 12p11.21-12p11.23 from telomeric to centromeric direction.

INTS13 (aka ASUN) (615079)

KS+NDD

12p11.23

Involved in regulation of mitotic cell cycle

Two nonsense^45,133, one synonymous²⁷, and one missense¹³⁴ variants in NDD patients

Critical regulator of spermatogenesis in Drosophila⁹⁸

Germline expression of mouse Asun rescued sterility and dynein mislocalization in Asun mutant flies⁹⁹

TM7SF3 (605181)

NDD

12p11.23

Involved in the inhibition of cytokine-induced death of pancreatic beta cells

Five missense^{27,38,134,135} variants in NDD patients

TM7SF3 is interacting with HNRNPL³⁹, a gene involved in ID⁴⁰

STK38L (615836)

NDD

12p11.23

Involved in the regulation of structural processes in differentiating and mature neuronal cells

Two missense^46,134, one synonymous^134,135 and one nonsense⁴⁵ variants in NDD patients

arbor-specific changes in dendritic complexity seen in the hippocampus of Stk38l KO mice⁴¹

ARNTL2 (2614517)

NDD

12p11.23

Transcriptional activator, which forms a core component of the circadian clock

One synonymous¹³⁵, two missense^47,134, and one nonsense⁴⁸ variants in NDD patients

ARNTL2 is interacting with CTTNBP2⁴⁹, UBE3A⁵¹, and PER2⁵⁵, three genes involved in NDDs

PPFIBP1 (603141)

KS+NDD

12p11.22-p11.23

May regulate the disassembly of focal adhesions

Four nonsense¹³⁶, two missense^134,135,136, one splice¹³⁶, and three frameshift^136,137 variants in NDD patients

PPFIBP1 is interacting with TACR3⁵⁵, a gene involved in HH with or without anosmia¹⁰⁰

PPFIBP1 is interacting with YWHAG⁵⁵, KRAS⁶⁰, NRAS¹⁰¹, HRAS¹⁰¹, CUL3¹⁰², and SNAP29⁵⁵, six genes involved in NDDs

REP15 (610848)

KS+NDD

12p11.22

Regulates transferrin receptor recycling from the endocytic recycling compartment

Rep15 KO Mice have an abnormal behavior phenotype (http://www.informatics.jax.org/marker/MGI:1913782)

REP15 is interacting with TLK2⁵⁵, a gene involved in NDD¹¹⁰, ASD⁵⁸, ID¹³⁸, and Schizophrenia¹¹¹

REP15 is interacting with SLC4A2⁵⁵. Slc4a2 KO Mice revealed an interruption in spermiogenesis leading to infertility¹⁰⁹

FAR2 (616156)

KS+NDD

12p11.22

Catalyzes the reduction of saturated but not unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols

One missense^134,135 variant in unrelated NDD patients

FAR2 interacts with PEX19^38,59,91, a gene involved in NDDs^27,38

FAR2 is interacting with ZP2⁵⁵, a gene related to oocyte maturation defect leading to female infertility¹¹³. Homozygous Zp2 -/- mouse females were sterile¹¹⁴

FAR2 is interacting with GRPR⁵⁹, a gene disrupted at the breakpoint in a patient⁴⁶, XX, t(X;8)(p22.13;q22.1) with autism and multiple exostoses¹³⁹

FAR2 is interacting with GRPR²⁹. GRPR deficient mice exhibits decreased inhibition of principal neurons, enhanced long-term potentiation (LTP), and greater and more persistent long-term fear memory¹⁴⁰

ERGIC2 (612236)

NDD

12p11.22

Possible role in transport between endoplasmic reticulum and Golgi

One missense¹³⁴, and one frameshift⁵⁸ variants in NDD patients

ERGIC2 is interacting with SLC39A8^55,59, CUX1⁶⁰, RAB3GAP1⁶⁰, and RAB3GAP2⁶⁰, four genes involved in NDDs

TMTC1 (615855)

NDD

12p11.22

Transfers mannosyl residues to the hydroxyl group of serine or threonine residues

One missense^27,38, one synonymous¹³⁴, and one splice¹³⁴ variants in NDD patients

TMTC1 is interacting with BCOR⁷², and VIRMA⁷³, two genes involved in NDDs

TSPAN11 tetraspanin 11

KS

12p11.21

Integral membrane protein, regulating cell adhesion, motility, and synapse formation, interacts with integrins

One missense³⁷ variant in KS patient

DENND5B (617279)

NDD

12p11.21

Guanine nucleotide exchange factor (GEF) which may activate RAB39A and/or RAB39B

One synonymous¹³⁵, and one missense^26,27,45,117 variants in NDD patients

DENND5B is interacting with RAB11A⁶⁰, and GRB10⁸⁴, two genes involved in NDDs

ETFBKMT (615256)

NDD

12p11.21

Enables heat shock protein binding activity and protein-lysine N-methyltransferase activity

One missense^134,135 and one synonymous^27,134,135 variants in NDD patients

ETFBKMT is interacting with TUBB2A⁹⁰, TUBB4A⁹⁰, DARS2⁵⁵, and GLS⁹¹, four genes involved in NDDs